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Treatment with Investigational LentiGlobin Gene Therapy for Sickle Cell Disease (bb1111) Results in Complete Elimination of SCD-Related Severe…

By adminDecember 8, 2020Stem Cell Medicine

CAMBRIDGE, Mass.--(BUSINESS WIRE)--bluebird bio, Inc. (Nasdaq: BLUE) announced that new data from Group C of its ongoing Phase 1/2 HGB-206 study of investigational LentiGlobin gene therapy (bb1111) for adult and adolescent patients with sickle cell disease (SCD) show a complete elimination of severe VOEs and VOEs between six and 24 months of follow-up. These data are being presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually from December 5-8, 2020.

Now with more than two years of data, we continue to observe promising results in our studies of LentiGlobin for SCD that further illustrate its potential to eliminate the symptoms and devastating complications of sickle cell disease. Consistently achieving the complete resolution of severe vaso-occlusive events (VOEs) and VOEs between Month 6 and Month 24 follow-up is unprecedented other than with allogeneic stem cell transplantation. Importantly, our data show the potential for LentiGlobin for SCD to produce fundamentally disease-modifying effects with sustained pancellular distribution of gene therapy-derived anti-sickling HbAT87Q and improvement of key markers of hemolysis that approach normal levels, said David Davidson, M.D., chief medical officer, bluebird bio. In addition to these clinical outcomes, for the first time with a gene therapy we now have patient-reported outcomes through the validated PROMIS-57 tool, showing reduction in pain intensity at 12 months after treatment with LentiGlobin for SCD. These results provide insight into the potential real-life impact LentiGlobin for SCD may offer patients.

SCD is a serious, progressive and debilitating genetic disease. In the U.S., the median age of death for someone with sickle cell disease is 43 46 years. SCD is caused by a mutation in the -globin gene that leads to the production of abnormal sickle hemoglobin (HbS). HbS causes red blood cells to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and unpredictable, painful VOEs.

In the HGB-206 study of LentiGlobin for SCD, VOEs are defined as episodes of acute pain with no medically determined cause other than a vaso-occlusion, lasting more than two hours and severe enough to require care at a medical facility. This includes acute episodes of pain, acute chest syndrome (ACS), acute hepatic sequestration and acute splenic sequestration. A severe VOE requires a 24-hour hospital stay or emergency room visit or at least two visits to a hospital or emergency room over a 72-hour period, with both visits requiring intravenous treatment.

LentiGlobin for SCD was designed to add functional copies of a modified form of the -globin gene (A-T87Q-globin gene) into a patients own hematopoietic (blood) stem cells (HSCs). Once patients have the A-T87Q-globin gene, their red blood cells can produce anti-sickling hemoglobin (HbAT87Q) that decreases the proportion of HbS, with the goal of reducing sickled red blood cells, hemolysis and other complications.

As a hematologist, I regularly see the debilitating effects of pain events caused by sickle cell disease. Pain has an overwhelmingly negative impact on many facets of my patients lives and can lead to prolonged hospitalizations, said presenting study author Alexis A. Thompson, M.D., professor of pediatrics at Northwestern University Feinberg School of Medicine and head of hematology at Ann and Robert H. Lurie Childrens Hospital of Chicago. The results observed with LentiGlobin gene therapy for SCD include the complete elimination of severe vaso-occlusive pain episodes, which is certainly clinically meaningful, but also for the first time, we have documented patients reporting that they are experiencing improved quality of life. This degree of early clinical benefit is extraordinarily rewarding to observe as a provider."

As of the data cut-off date of August 20, 2020, a total of 44 patients have been treated with LentiGlobin for SCD in the HGB-205 (n=3) and HGB-206 (n=41) clinical studies. The HGB-206 total includes: Groups A (n=7), B (n=2) and C (n=32).

HGB-206: Group C Updated Efficacy Results

The 32 patients treated with LentiGlobin for SCD gene therapy in Group C of HGB-206 had up to 30.9 months of follow-up (median of 13.0; min-max: 1.1 30.9 months).

In patients with six or more months of follow-up whose hemoglobin fractions were available (n=22), median levels of gene therapy-derived anti-sickling hemoglobin, HbAT87Q, were maintained with HbAT87Q contributing at least 40% of total hemoglobin at Month 6. At last visit reported, total hemoglobin ranged from 9.6 15.1 g/dL and HbAT87Q levels ranged from 2.7 8.9 g/dL. At Month 6, the production of HbAT87Q was associated with a reduction in the proportion of HbS in total hemoglobin; median HbS was 50% and remained less than 60% at all follow-up timepoints. All patients in Group C were able to stop regular blood transfusions by three months post-treatment and remain off transfusions as of the data cut-off.

Nineteen patients treated in Group C had a history of severe VOEs, defined as at least four severe VOEs in the 24 months prior to informed consent (annualized rate of severe VOE min-max: 2.0 10.5 events) and at least six months follow-up after treatment with LentiGlobin for SCD. There have been no reports of severe VOEs in these Group C patients following treatment with LentiGlobin for SCD. In addition, all 19 patients had a complete resolution of VOEs after Month 6.

Hemolysis Markers

In SCD, red blood cells become sickled and fragile, rupturing more easily than healthy red blood cells. The breakdown of red blood cells, called hemolysis, occurs normally in the body. However, in sickle cell disease, hemolysis happens too quickly due to the fragility of the red blood cells, which results in hemolytic anemia.

Patients treated with LentiGlobin for SCD in Group C demonstrated near-normal levels in key markers of hemolysis, which are indicators of the health of red blood cells. Lab results assessing these indicators were available for the majority of the 25 patients with 6 months of follow-up.

The medians for reticulocyte counts (n=23), lactate dehydrogenase (LDH) levels (n=21) and total bilirubin (n=24) continued to improve compared to screening values and stabilized by Month 6. In patients with Month 24 data (n=7), these values approached the upper limit of normal by Month 24. These results continue to suggest that treatment with LentiGlobin for SCD may improve biological markers to near-normal levels for SCD.

Pancellularity

As previously reported, assays were developed by bluebird bio to enable the detection of HbAT87Q and HbS protein in individual red blood cells, as well as to assess if HbAT87Q was pancellular, or present throughout all of a patients red blood cells. In 25 patients with at least six months of follow-up, on average, more than 80% of red blood cells contained HbAT87Q, suggesting near-complete pancellularity of HbAT87Q distribution and with pancellularity further increasing over time.

HGB-206: Improvements in Health-Related Quality of Life

Health-related quality of life (HRQoL) findings in Group C patients treated with LentiGlobin for SCD in the HGB-206 study were generated using the Patient Reported Outcomes Measurement Information System 57 (PROMIS-57), a validated instrument in SCD.

Data assessing pain intensity experienced by nine Group C patients were analyzed according to baseline pain intensity scores relative to the general population normative value: 2.6 on a scale of 0-10, where 10 equals the most intense pain. Data were assessed at baseline, Month 6 and Month 12.

Of the five patients with baseline scores worse than the population normative value average, four demonstrated clinically meaningful reductions in pain intensity at Month 12; the group had a mean score of 6.0 at baseline and a mean score of 2.4 at Month 12. Of the four patients with better than or near population normative values at baseline, two reported improvement and two remained stable with a mean score of 2.3 at baseline and 0.8 at Month 12.

HGB-206: Group C Safety Results

As of August 20, 2020, the safety data from Group C patients in HGB-206 remain generally consistent with the known side effects of hematopoietic stem cell collection and myeloablative single-agent busulfan conditioning, as well as underlying SCD. One non-serious, Grade 2 adverse event (AE) of febrile neutropenia was considered related to LentiGlobin for SCD. There were no serious AEs related to LentiGlobin for SCD.

One patient with significant baseline SCD-related and cardiopulmonary disease died 20 months post-treatment; the treating physician and an independent monitoring committee agreed his death was unlikely related to LentiGlobin for SCD and that SCD-related cardiac and pulmonary disease contributed.

LentiGlobin for SCD Data at ASH

The presentation of HGB-206 Group C results and patient reported outcomes research are now available on demand on the ASH conference website:

About HGB-206

HGB-206 is an ongoing, Phase 1/2 open-label study designed to evaluate the efficacy and safety of LentiGlobin gene therapy for sickle cell disease (SCD) that includes three treatment cohorts: Groups A (n=7), B (n=2) and C (n=32). A refined manufacturing process designed to increase vector copy number (VCN) and further protocol refinements made to improve engraftment potential of gene-modified stem cells were used for Group C. Group C patients also received LentiGlobin for SCD made from HSCs collected from peripheral blood after mobilization with plerixafor, rather than via bone marrow harvest, which was used in Groups A and B of HGB-206.

About LentiGlobin for SCD (bb1111)

LentiGlobin gene therapy for sickle cell disease (bb1111) is an investigational treatment being studied as a potential treatment for SCD. bluebird bios clinical development program for LentiGlobin for SCD includes the completed Phase 1/2 HGB-205 study, the ongoing Phase 1/2 HGB-206 study, and the ongoing Phase 3 HGB-210 study.

The U.S. Food and Drug Administration granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation and rare pediatric disease designation for LentiGlobin for SCD.

LentiGlobin for SCD received orphan medicinal product designation from the European Commission for the treatment of SCD, and Priority Medicines (PRIME) eligibility by the European Medicines Agency (EMA) in September 2020.

bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-307) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for SCD. For more information visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov and use identifier NCT04628585 for LTF-307.

LentiGlobin for SCD is investigational and has not been approved in any geography.

About bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, were developing gene and cell therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, were working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. Were putting our care and expertise to work across a spectrum of disorders: cerebral adrenoleukodystrophy, sickle cell disease, -thalassemia and multiple myeloma, using gene and cell therapy technologies including gene addition, and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

LentiGlobin and bluebird bio are trademarks of bluebird bio, Inc.

Forward-Looking Statements

This release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Any forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: regarding the potential for LentiGlobin for Sickle Cell Disease to treat SCD; the risk that the efficacy and safety results from our prior and ongoing clinical trials will not continue or be repeated in our ongoing or planned clinical trials; the risk that the current or planned clinical trials of our product candidates will be insufficient to support regulatory submissions or marketing approval in the United States and European Union; the risk that regulatory authorities will require additional information regarding our product candidates, resulting in delay to our anticipated timelines for regulatory submissions, including our applications for marketing approval; and the risk that any one or more of our product candidates, will not be successfully developed, approved or commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in our most recent Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.

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Treatment with Investigational LentiGlobin Gene Therapy for Sickle Cell Disease (bb1111) Results in Complete Elimination of SCD-Related Severe...

Anatomy of a vaccine: What it takes to create a safe, effective COVID shot – University of California

By adminDecember 8, 2020Stem Cell Medicine

Shawn stepped into the UCLA Vine Street Clinic in Hollywood with confidence. He offered up his arm. The UCLA doctor injected him. It took seconds; there was barely a sting.

Twenty-four hours after the first of two shots, given 28 days apart, he suffered the headaches and fatigue associated with a milder case of COVID-19. But Shawn remained calm, resolved to honor the memory of his mother, a nurse who had died in May 2020 from an unrelated cause.

The 57-year-old nonprofit worker had been thinking about the challenges of COVID-19 for a long time, and he decided to go through the lengthy consent process for the medical trial. It gave me something to do with my anger that was so much better than yelling at someone for not wearing a mask, he says. And [at UCLA] I felt I was in good hands.

Shawn is one of many volunteers who have stepped up to participate in medical trials at UCLA, which is part of a global network thats determined to help find a vaccine against the novel coronavirus.

The stakes are huge. More than 250,000 Americans have already died, and there have been more than 1 million deaths around the world. Economies have been brought to their knees, social tensions have disrupted communities and emotional maladies are on the rise.

In response, doctors and scientists have been challenged to be resilient and ingenious. Theyre taking an array of different approaches, knowing that public confidence in vaccines hangs in the balance.

In addition, it has been a challenge to create a vaccine in such a short amount of time similar efforts have taken five to 10 years. Pharmaceutical giant Pfizer and biotech firm Moderna have both reported remarkable progress, announcing in November that their vaccine candidates were more than 90% effective. All of which has raised questions about the next steps, such as how the vaccines will be distributed.

I dont want to make a vaccine to protect against mild disease, says Dr. Marcus Horwitz, distinguished professor of medicine and microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA. I want to protect people who are going to get severe disease.

Horwitz has already developed vaccines against the bacteria behind tuberculosis, anthrax and the tick-borne disease tularemia, but he has never tried to create a vaccine against a virus. When faced with a worldwide pandemic, we thought we might be able to make a contribution, he says.

Vaccines work by training the immune system to recognize and fight disease-causing pathogens, such as viruses or bacteria. Doctors introduce the bodys immune system to antigens, which are molecules from the virus or bacteria, and the immune system responds by making proteins called antibodies and immunity-building T cells, which both neutralize the pathogen.

The delivery of these antigens requires a delicate calculus: It must provoke the immune system, but not go so far as to make the patient ill. You need a vector that will wake up the immune system of the host, but not cause any further harm, Horwitz says.

The vaccine approach by Horwitz and his team, including lead investigator Qingmei Jia, is a medical outlier: They adapted an existing antibacterial platform to build protection against SARS-CoV-2, the virus that causes COVID-19. The team has shown that their vaccine candidate protects hamsters, which develop severe disease in a way similar to humans.

Some of the potential vaccines for SARS-CoV-2 use a weakened form of an adenovirus, which causes the common cold, to deliver the S protein that is found on the surface of the SARS-CoV-2 virus. Horwitzs vaccine stands out from the pack because it uses a weakened bacterium to deliver two SARS-CoV-2 proteins, the M and N proteins.

That difference could have a tremendous impact. Billions of COVID-19 vaccine doses are needed, and bacteria, unlike viruses, are easy and cheap to produce and transportable.

The success of a COVID-19 vaccine also depends on the immune system, which can be less robust in older people.

This is a problem that has driven Song Li, chair of the bioengineering department at the UCLA Samueli School of Engineering, who has focused his career on cell and tissue engineering. Adapting a concept from cancer immunotherapy, Li is developing a biomaterial vaccine booster using artificial cells that could improve the immune systems ability to generate long-term protection.

When the immune system encounters a destructive pathogen, it produces cells that are designed to attack the invader. A small number of those cells, called T memory stem cells, can stay in the system for years ready for a future invasion. Unfortunately, our ability to produce T memory stem cells declines as we get older. Li hopes his booster, in combination with a vaccine, can help fragile immune systems effectively fight against the SARS-CoV-2 virus.

My goal at the outset was to help the elderly population, Li says. But it could be useful for any person whose immune system needs help generating protection from the virus.

Another UCLA team led by Bogdan Pasaniuc, Dr. Manish Butte and Dr. Daniel Geschwind, the Gordon and Virginia MacDonald Distinguished Professor of Human Genetics at the Geffen School of Medicine is trying to find out why the virus significantly impacts some, but leaves others relatively unscathed.

We know age is a major factor, but we see older people who get infected and do quite well, Geschwind says. We have a limited ability to predict how sick someone will get. His team hopes that studying whole-genome sequences from thousands of COVID-19 patients will reveal hidden factors that make some more vulnerable than others. The research could help identify people who are at higher risk for infection as well as develop new treatment and prevention strategies.

Dr. Brigitte Gomperts, professor of pediatrics and pulmonary medicine and a member of the UCLA Broad Stem Cell Research Center, is studying how COVID-19 affects lung tissue. By using stem cellderived clusters of lung cells, known as organoids, she can rapidly screen thousands of prospective treatments. Because the organoids are grown from human cells and reflect the cell types and architecture of the lungs, they can offer insights into how the virus infects and damages the organ.

At UCLA medical centers around Los Angeles County, physicians are ensuring that their medical trials include diverse groups of people and women of all ages.

COVID-19 has hit the African American and Latino communities particularly hard, says Dr. Jesse Clark, associate professor-in-residence in the department of medicine at the Geffen School of Medicine. We have to make sure that any vaccine has been determined to be safe and effective in all populations that will receive it.

COVID-19 has hit the African American and Latino communities particularly hard. We have to make sure that any vaccine has been determined to be safe and effective in all populations that will receive it.

Dr. Jesse Clark, associate professor-in-residence in the department of medicine at the David Geffen School of Medicine at UCLA

Clark is medical director of the UCLA Vine Street Clinic, which is involved in the Moderna clinical trial. Notably, Modernas vaccine works differently from a typical vaccine, because it doesnt contain the virus at all. Instead, it uses messenger RNA, or mRNA, which uses the bodys genetic code to produce antibodies against the virus.

CNN mentioned that the vaccine trials were having trouble finding minorities to participate, says Roderick, a 37-year-old IT manager and father of two, who is participating in the Moderna trial. Being Black and Mexican, and knowing how hard my demographic has been hit, I just went ahead and signed up online. Its worth doing to help out.

Meanwhile, Dr. Katya Corado, an infectious disease specialist at Harbor-UCLA Medical Center in Torrance, has been enrolling patients in a phase 3 clinical trial of an adenovirus vector vaccine thats under development by the University of Oxford and the biopharmaceutical company AstraZeneca.

All vaccines undergo three phases of clinical trials, according to rules set by the Food and Drug Administration. Phase 1, which involves 20 to 100 volunteers, tests the safety and dosage of the vaccine. Phase 2 tests the drugs efficacy and side effects among several hundred participants, and phase 3 gathers more information about a vaccines safety and effectiveness by studying thousands of volunteers.

In the phase 3 trial, we focus on studying how effective the vaccine is in populations that need it most, Corado says.

Clark and Corado are both hopeful that their work can protect the most vulnerable, which includes people over 65, patients with chronic conditions, those facing economic disadvantages and essential workers.

Inoculations have eradicated past epidemics, such as smallpox. But public faith in vaccines has wavered, especially when a now-disproven report in 1998 suggested that the measles, mumps and rubella vaccine was linked to autism spectrum disorder. That has led to U.S. outbreaks of measles, which had been previously eliminated. So scientists recognize the importance of getting the COVID-19 vaccine right.

There are other factors to consider as well. Vaccine distribution will be high on the agenda of the incoming White House administration, but if supply is limited, the Centers for Disease Control and Prevention recommends prioritizing certain groups, such as medical workers.

Also, some vaccines currently in development need to be stored in ultra-cold conditions. For example, Pfizers vaccine must be stored at minus 70 degrees Celsius, while Modernas vaccine must be kept at minus 20 degrees Celsius the temperature of a regular freezer. These factors will affect how the vaccines are distributed.

Some lawmakers have advocated letting the virus run its course in the hopes of achieving herd immunity, which is when enough people have become immune to an infectious disease, either through being infected or vaccination. Since the COVID-19 vaccine is still pending, a majority of people will need to be infected in order to achieve herd immunity and that comes at a terrible cost.

According to Dr. Robert Kim-Farley, professor-in-residence of epidemiology at the UCLA Fielding School of Public Health, up to 2 million Americans would have to die before the country reached herd immunity.

He argues that vaccines work, even if they are not perfectly safe or perfectly effective, as proven by the near-eradication of polio. But approving vaccines prematurely to buckle under the pressure of politics or profit could cause a terrible backlash against being vaccinated, which could lead to future outbreaks.

We want to make sure we are not cutting corners, Kim-Farley says, that we are getting the best vaccine that has the highest efficacy, the longest duration, the fewest number of side effects [with] the fewest number of doses.

This is a very high-stakes game, and its important to get it right, without recalls or playing into the [anti-vaccination] narrative. What still concerns me is the equitable distribution of vaccines to make sure that countries that are not as wealthy as us have access to these life-saving vaccines. We are all members of one global community.

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Anatomy of a vaccine: What it takes to create a safe, effective COVID shot - University of California

Magenta Therapeutics Announces Commencement of First Phase 2 Clinical Trial of MGTA-145 for Stem Cell Mobilization, Oral Presentation of MGTA-145…

By adminDecember 8, 2020Stem Cell Medical Center

Dec. 7, 2020 13:00 UTC

Enrollment commenced in the MGTA-145 Phase 2 clinical trial of autologous transplant of multiple myeloma patients at Stanford University

Oral presentation of Phase 1 clinical data presented at the 62nd American Society of Hematology (ASH) Annual Meeting confirming MGTA-145 achieved proof-of concept: all safety and efficacy endpoints met and mobilized cells demonstrated functional superiority over other mobilization approaches in preclinical studies

Preclinical data from MGTA-117, the first targeted antibody-drug conjugate (ADC) from the Magenta platform, continue to indicate that it is an effective, potent conditioning agent with the potential to improve transplant outcomes in patients with blood cancers and genetic diseases

Magenta expects to provide additional updates on its programs and clinical plans in early 2021

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplant to more patients, today announced final clinical results from its earlier completed Phase 1 clinical trial as well as development updates for its MGTA-145 stem cell mobilization therapy, including commencement of enrollment in a Phase 2 clinical trial in multiple myeloma, and its plans for a Phase 2 clinical trial in allogeneic stem cell transplant for patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndrome (MDS). The company also previously announced a clinical collaboration with bluebird bio to evaluate MGTA-145 for mobilizing and collecting stem cells in adults and adolescents with sickle cell disease (SCD). Additional preclinical results were also presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually from December 5-8, 2020, on the Magenta conditioning platform, including MGTA-117 program, which is a targeted antibody-drug conjugate (ADC) to prepare patients for stem cell transplant.

MGTA-145 Advancement to Phase 2 Development in Blood Cancers

The company announced that enrollment has started and is ongoing in a Phase 2 clinical trial of MGTA-145, used in combination with plerixafor, to mobilize and collect stem cells for autologous stem cell transplantation of multiple myeloma patients at Stanford University. Magenta expects that this trial will provide patient-level data on stem cell mobilization and collection, characteristics of the mobilized graft and engraftment in patients with multiple myeloma.

Additionally, through a collaboration with the National Marrow Donor Program/Be The Match, a global leader in facilitating allogeneic hematopoietic stem cell transplantation, Magenta plans to initiate a Phase 2 clinical trial in early 2021 using MGTA-145 to mobilize and collect stem cells from allogeneic donors for transplant in patients with AML, ALL and MDS. Allogeneic stem cell transplant provides a potentially curative therapeutic option for patients with these diseases. This clinical trial will evaluate stem cell mobilization, collection, cell quality, engraftment and the potential for reduced Graft-versus-Host Disease (GvHD), which is of particular importance in the allogeneic transplant setting.

MGTA-145 in Sickle Cell Disease

Magenta Therapeutics recently announced an exclusive clinical collaboration with bluebird bio to evaluate the utility of MGTA-145, in combination with plerixafor, for the mobilization and collection of stem cells in adults and adolescents with SCD.

The data from this clinical trial could provide proof-of-concept for MGTA-145, in combination with plerixafor, as the preferred mobilization regimen for patients with SCD. bluebird bios experience with plerixafor as a mobilization agent in SCD aligns with Magentas combination therapy approach, utilizing MGTA-145 plus plerixafor with potential for safe, rapid and reliable mobilization of sufficient quantities of high-quality stem cells to improve outcomes associated with stem cell transplantation.

MGTA-145 Presentations at ASH

Magenta presented final clinical data from its MGTA-145 stem cell mobilization Phase 1 clinical trial in healthy volunteers at the ASH Annual Meeting. All primary and secondary endpoints were met in the study completed earlier this year.

The results demonstrate that a single dose of MGTA-145, in combination with plerixafor, rapidly and reliably mobilized high numbers of stem cells in a single day without the need for G-CSF for potential use in diseases that can benefit from autologous and/or allogeneic stem cell transplantation. The additional data also offer further confirmation that MGTA-145, in combination with plerixafor, was well tolerated and provides a rapid and reliable method to obtain large numbers of hematopoietic stem cells. Transplant of these cells in preclinical models resulted in enhanced, durable engraftment, in addition to highly immunosuppressive properties, leading to reduced GvHD.

Results from this study provide a robust dataset and proof of concept that MGTA-145, in combination with plerixafor, provides rapid and robust mobilization of stem cells and that these cells have better engraftment potential, are able to be gene modified and engraft and reduce GvHD in preclinical models compared to cells mobilized with other available agents. The data reinforce the availability of compelling opportunities for development in both the autologous and allogeneic transplant settings, said John Davis Jr., M.D., M.P.H., M.S., Head of Research & Development and Chief Medical Officer, Magenta Therapeutics.

The data were presented by Steven M. Devine, MD, Chief Medical Officer of the National Marrow Donor Program/Be The Match and Associate Scientific Director of the CIBMTR (Center for International Blood and Marrow Transplant Research).

Conditioning Program (MGTA-117 and CD45-ADC) Presentations at ASH

Magenta also provided updates on its conditioning platform at the ASH Annual Meeting, including MGTA-117 and CD45-ADC programs. Preclinical data from a study of MGTA-117 demonstrate that it is an effective, potent conditioning agent for transplant with anti-leukemic activity, significantly decreasing tumor burdens, leading to delayed tumor growth and increased median survival rates in animal models of AML. Ongoing GLP toxicology and GMP manufacturing progress continue to be supportive of advancing MGTA-117 towards an IND filing in AML and MDS.

Additionally, preclinical data from a study of Magentas CD45-ADC, a CD45-targeted conditioning agent designed to remove the cells that cause autoimmune diseases to enable curative immune reset, demonstrated the ability to achieve successful outcomes as a single agent in the most challenging disease model through fully mismatched allogeneic hematopoietic stem cell transplant, where only radiation or combinations of toxic chemotherapies are available, potentially providing patients the option of a reduced toxicity conditioning regimen. The company continues to evaluate this program preclinically.

About MGTA-145

MGTA-145 is being developed in combination with plerixafor to harness complementary chemokine mechanisms to mobilize hematopoietic stem cells for collection and transplantation. This new combination has the potential to be the preferred mobilization regimen for rapid and reliable mobilization and collection of hematopoietic stem cells to improve outcomes in autologous and allogeneic stem cell transplantation, which can rebuild a healthy immune system for patients with blood cancers, genetic diseases and autoimmune disorders.

MGTA-145 has the potential to replace the current standard of care for patients and allogeneic donors who currently rely on the use of granulocyte-colony stimulating factor (G-CSF) alone or in combination with plerixafor, which can take up to five days or longer to mobilize sufficient numbers of stem cells, often resulting in significant bone pain and other side effects.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with blood cancer, genetic diseases and autoimmune diseases. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients.

Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com.

Follow Magenta on Twitter: @magentatx.

Forward-Looking Statement

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavor, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation risks set forth under the caption Risk Factors in Magentas Annual Report on Form 10-K filed on March 3, 2020, as updated by Magentas most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Magenta Therapeutics Announces Commencement of First Phase 2 Clinical Trial of MGTA-145 for Stem Cell Mobilization, Oral Presentation of MGTA-145...

Precigen Presents New Data Supporting the Safety, Clinical Activity, Expansion and Persistence of PRGN-3006 UltraCAR-T at the 62nd ASH Annual Meeting…

By adminDecember 8, 2020Stem Cell Medical Center

GERMANTOWN, Md., Dec. 7, 2020 /PRNewswire/ -- Precigen Inc., a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, today announced at the 62nd ASH Annual Meeting and Exposition (Abstract 2864) clinical progress and new data from the ongoing Phase 1/1b clinical study of PRGN-3006UltraCAR-Tin patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) and higher risk myelodysplastic syndrome (MDS) (clinical trial identifier: NCT03927261).

AML is a rapidly progressing disease with poor prognosis and high unmet need. Precigen's UltraCAR-T platform is designed to overcome limitations of currently available chimeric antigen receptor (CAR)-T therapies by utilizing an advanced overnight non-viral gene delivery manufacturing process at a medical center's cGMP facility without the need for ex vivo expansion. Current CAR-T cell therapies are limited due to, inter alia, the prolonged interval between apheresis to product infusion and an exhausted phenotype of T cells resulting from lengthy ex vivo expansion. As announced in November 2020, UltraCAR-T cells for the PRGN-3006 study are now manufacturedovernight using Precigen's proprietary UltraPorator device. PRGN-3006 UltraCAR-T is a multigenic autologous CAR-T simultaneously expressing a CAR specifically targeting CD33; membrane bound IL-15 (mbIL15) for enhanced in vivo expansion and persistence; and a kill switch to conditionally eliminate CAR-T cells for an improved safety profile. CD33 is over-expressed on AML blasts with lesser expression on normal hematopoietic stem cells.

An investigator-initiated, non-randomized Phase 1/1b dose-escalation study to evaluate the safety and maximal tolerated dose of PRGN-3006 UltraCAR-T is currently ongoing in collaboration with the H. Lee Moffitt Cancer Center & Research Institute (Moffitt). The study population includes adult patients ( 18 years) with r/r AML and hypomethylating agent (HMA) failure, higher risk MDS or chronic myelomonocytic leukemia (CMML) patients with 5% blasts. To test the hypothesis that expression of mbIL15 on PRGN-3006 can promote UltraCAR-T cell expansion and persistence without the need for lymphodepletion and improve the overall safety profile, studysubjects receive the PRGN-3006 infusion either without prior lymphodepletion (Cohort 1) or following lymphodepleting chemotherapy (Cohort 2). A multicenter expansion of the trial is planned.

Key findings:

A case study of the patient with the longest follow-up as of the data cutoff was also presented. This patient received, one day after gene transfer and without prior lymphodepletion, a very low dose, approximately three hundred thousand UltraCAR-T per kilogram (3 x 105 UltraCAR-T/kg) for a total of only 24 million UltraCAR-T. She is a 69 year old female with secondary AML (sAML) and four prior lines of therapy, including induction chemotherapy (IC), allogenic hematopoietic stem cell transplantation (allo-HSCT), HMA plus venetoclax (HMA+VEN), refractory to all therapy post allo-HSCT. The patient had approximately 40% peripheral blasts and 47% bone marrow blasts at baseline.

Case study findings:

"There is an urgent need for novel therapies for relapsed or refractory AML patients as the median overall survival for this patient population is less than six months. Current CAR-T approaches for AML have faced challenges due to long manufacturing durations resulting in subsequent delays in treatment," said David A. Sallman, MD, of Moffitt and lead investigator for the PRGN-3006 clinical study. "We are encouraged by the initial data, including safety and manufacturing success from patients treated with autologous UltraCAR-T cells, which were manufactured on-site with almost instant turnaround. We are excited by the expansion and continued persistence of PRGN-3006 UltraCAR-T cells in the patient case study for over seven months post-infusion without prior lymphodepletion and are looking forward to higher doses in the lymphodepleted and non-lymphodepletion cohorts."

"Currently commercialized CAR-T therapies have not demonstrated the persistence needed to drive sustained, durable responses," said Helen Sabzevari, PhD, President and CEO of Precigen. "The results from Dr. Sallman's patient case study are particularly encouraging as the patient received a very low dose of cells without any ex vivo expansion or activation and no lymphodepletion, which highlights the importance of membrane bound IL-15 in expansion and persistence of these cells and, we believe, differentiates the UltraCAR-T platform from other CAR-T's. In particular, expansion and persistence of UltraCAR-T cells in the patient's blood through seven months post-infusion show promise for the durability of PRGN-3006. We look forward to providing additional details for the PRGN-3006 study at our upcoming clinical update call this month."

About Acute Myeloid Leukemia (AML) AML is a cancer that starts in the bone marrow, but most often moves into the blood.1 Though consideredrare, AML is among the most common types of leukemia in adults.2 In 2019, it was estimated that 21,450 new cases of AML would be diagnosed in the US.2 AML is uncommon before the age of 45 and the average age of diagnosis is about 68.2 The prognosis for patients with AML is poor with an average 5year survival rate of approximately 25 percent overall, and less than a 5 percent 5year survival rate for patients older than 65.3 Amongst elderly AML patients ( 65 years of age), median survival isshort, ranging from 3.5 months for patients 65 to 74 years of age to 1.4 months for patients 85 years of age.3

About Myelodysplastic Syndrome (MDS) MDS are diseases of the bone marrow generally found in adults in their 70s.4 Incidence in the US is not known for sure, but estimates range from 10,000 each year and higher.4 Using International Prognostic Scoring System (IPSS-R), median survival for MDS patients can vary from less than one year for the "very high" IPSS-R risk group to more than eight years for the "very low" IPSS-R group.4

About PRGN-3006 UltraCAR-T PRGN-3006 UltraCAR-T is a multigenic autologous CAR-T cell treatment utilizing Precigen's non-viral Sleeping Beauty system to simultaneously express a CAR specifically targeting CD33, which is over expressed on acute myeloid leukemia blasts with lesser expression on normal hematopoietic stem cell populations and minimal non-hematopoietic expression; membrane bound IL-15 for enhanced in vivo expansion and persistence; and a kill switch to conditionally eliminate CAR-T cells for animproved safety profile. PRGN-3006 is being evaluated in collaboration with the Moffitt Cancer Center in a nonrandomized, investigatorinitiated Phase 1/1b dose escalation study to evaluate the safety and maximal tolerated dose of PRGN3006 UltraCAR-T (clinical trial identifier: NCT03927261). The study population includes patients with relapsed or refractory acute myeloid leukemia or higher risk myelodysplastic syndrome. The US Food and Drug Administration (FDA) has granted orphan drug designation (ODD) for PRGN-3006 UltraCAR-T in patients with AML.

Precigen: Advancing Medicine with Precision Precigen (Nasdaq: PGEN) is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated unique therapies toward clinical proof-of-concept and commercialization. For more information about Precigen, visit http://www.precigen.com or follow us on Twitter @Precigen and LinkedIn.

Trademarks Precigen, UltraCAR-T, UltraPorator and Advancing Medicine with Precision are trademarks of Precigen and/or its affiliates. Other names may be trademarks of their respective owners.

Cautionary Statement Regarding Forward-Looking Statements Some of the statements made in this press release are forward-looking statements. These forward-looking statements are based upon the Company's current expectations and projections about future events and generally relate to plans, objectives, and expectations for the development of the Company's business, including the timing and progress of preclinical studies, clinical trials, discovery programs and related milestones, the promise of the Company's portfolio of therapies, and in particular its CAR-T therapies, and the Company's refocus to a healthcare-oriented business. Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable, all forward-looking statements involve risks and uncertainties, including the possibility that the timeline for the Company's clinical trials might be impacted by the COVID-19 pandemic, and actual future results may be materially different from the plans, objectives and expectations expressed in this press release. The Company has no obligation to provide any updates to these forward-looking statements even if its expectations change. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. For further information on potential risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in the Company's most recent Annual Report on Form 10-K and subsequent reports filed with the Securities and Exchange Commission.

References 1 American Cancer Society. What is Acute Myeloid Leukemia (AML)? 2 American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML) 3 Thein, M., et al., Outcome of older patients with acute myeloid leukemia: an analysis of SEER data over 3 decades. Cancer, 2013. 119(15): p.2720-7 4 American Cancer Society.Key Statistics for Myelodysplastic Syndromes

For more information, contact:

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SOURCE Precigen, Inc.

ALLO-715, Off-the-Shelf CAR T-Cell Therapy, Produces Early Promise in Multiple Myeloma – Cancer Network

By adminDecember 8, 2020Stem Cell Medical Center

Treatment with an off-the-shelf CAR T-cell therapy that targets B-cell maturation antigen (BCMA), ALLO-715, elicited responses in heavily pretreated patients with relapsed/refractory multiple myeloma in early findings from a first-in-human study presented at the 2020 ASH Meeting.1

The therapy generated responses in 6 of 10 patients (60%), including a very good partial-plus response (VGPR+) in 4 patients (40%), who were treated with ALLO-715 at a dose of 320 x 106 CAR cells plus a lymphodepleting regimen that included ALLO-647, an anti-CD52 monoclonal antibody, during the ongoing phase 1 UNIVERSAL study (NCT04093596).1

The findings mark the first results for an allogeneic CAR therapy directed at BCMA, said lead study author Sham Mailankody, MBBS, a medical oncologist and investigator in the Cellular Therapeutics Center at Memorial Sloan Kettering Cancer Center in New York, New York. BCMA, which is highly expressed on plasma and multiple myeloma cells, has sparked intensive research interest.2

These results demonstrate the feasibility and safety of an off-the-shelf CAR T cell therapy for multiple myeloma. In this first report of an allogeneic BCMA CAR T-cell therapy, we show that nearly 90% of patients were treated within 5 days of enrollment and without needing any bridging therapy, Mailankody said.

Allogeneic CAR therapy offers the potential for scalable manufacturing for on-demand treatment with shorter waiting times, which would overcome some of the logistical challenges posed by autologous CAR therapy, Mailankody said. The T cells needed for ALLO-715 are harvested from healthy donors and genetically engineered to express CARs aimed at specific cancer targets, according to Allogene Therapeutics, the company developing the therapy.3

ALLO-715 includes a human-derived single-chain variable fragment anti-BCMA cell with a 4-1BB costimulatory domain. Mailankody said the 2 key attributes of the construct are a knockout of CD52, which allows for selective lymphodepletion with ALLO-647 to prevent graft rejection without affecting the CAR T cells, and a knockout of the TRAC gene, which also minimizes the risk of graft-versus-host disease (GVHD).1

The UNIVERSAL study, which is being conducted at 11 cancer centers in the United States, is recruiting patients with multiple myeloma who have received 3 or more prior therapies, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 agent, and are refractory to their last treatment. Participants must have an ECOG performance status score of 0 or 1.

The dose escalation portion of the study is testing ALLO-715 as a single infusion across 4 doses: 40, 160, 320, or 480 x 106 CARs. Lymphodepletion regimens consist of fludarabine (F; 30 mg/m2/day) plus cyclophosphamide (C; 300 mg/m2/day) given on 3 days with ALLO-647 (A; 13-30 mg x 3 days; FCA) or cyclophosphamide plus ALLO-647 (CA).

Among the 35 patients enrolled at the time of the presentation, 4 became ineligible because of organ failure due to rapidly progressing disease. Of 31 patients in the safety population, the median age was 65 years (range, 46-76). Nearly half of the patients (48%) have high-risk cytogenetics and 23% had extramedullary disease. The efficacy population at data cutoff on October 30, 2020, comprised 26 patients across the 4 dosing levels, with a median follow-up of 3.2 months.1

The overall response rate (ORR) varied across dosing cohorts and lymphodepleting regimens. No responses were observed among 3 patients each who received CARs at 40 x 106 with FCA or 160 x 106 with CA, both with low-dose ALLO-647. The ORRs were 50% in 4 patients who received CARs at 160 x 106 with lowALLO-647 FCA; 33% in 3 at 480 x 106 with lowALLO-647 FCA; and 67% in 3 at 320 x 106 with lowALLO-647 CA.

The most robust responses were seen among those who received ALLO-647 at 320 x106. For this cohort, the ORR was 60% among 10 patients, including 3 of 6 who received CARs with lowALLO-647 FCA and 3 of 4 who had the therapy with highALLO-647 FCA. Overall, 6 patients had a VGPR+, defined as stringent complete response, complete response, or VGPR. These included 1 at 160, 4 at 320, and 1 at 480 10 x 106 CARs. Of the VGPR+ patients, 5 were negative for measurable residual disease. Additionally, 6 of 9 patients treated at the 320 or 480 x 106 dose levels remain in response.

Mailankody highlighted the experience of 1 participant, a 71-year-old man whose myeloma had progressed after undergoing 9 prior lines of therapy including autologous stem cell transplant and an experimental BCMA-targeted therapy. The patient received a conditioning regimen of FCA with low-dose ALLO-647 and ALLO-715 at 320 x 106. He reached a VGPR on day 14 that deepened to a stringent complete response by day 28 that remains in effect at 6 months, while experiencing grade 1 cytokine release syndrome (CRS).

The patient is clinically doing very well and is back at work, Mailankody said.

Among 31 patients in the safety population, most adverse effects were of grade 1 or 2 severity. These included CRS in 14 patients (45%) and infusion-related reactions to ALLO-647 in 7 patients (23%). The use of drugs to manage CRS also was low, at 19% for tocilizumab and 10% for steroids.

All-grade infections were reported in 13 patients (42%), including grade 3 events in 4 (13%). One patient (3%) died from a presumed fungal pneumonia related to progressive disease and the CA conditioning regimen but unrelated to ALLO-715. There were no instances of neurotoxicity or GVHD.

Notably, the fact that we did not see any GVHD is encouraging for an off-the-shelf allogeneic product, Mailankody said.

In response to a question from a conference attendee, Mailankody said it is too soon to compare efficacy levels seen with this allogeneic CAR therapy with those observed with investigational autologous CARs, which have been under study for several years.

Moving forward, investigators are continuing to evaluate dosing levels for ALLO-715. UNIVERSAL is enrolling patients to the 480 x 106 cohort, Mailankody said, adding that the appropriate dose likely would land between 320 and 480 x 106.

References

1. Mailankody S, Matous JV, Liedtke M, et al. Universal: an allogeneic first-in-human study of the anti-Bcma ALLO-715 and the Anti-CD52 ALLO-647 in relapsed/refractory multiple myeloma. Presented at: 2020 American Society of Hematology Annual Meeting and Exposition. December 5-8, 2020; Virtual. Abstract 129. Accessed December 5, 2020. https://ash.confex.com/ash/2020/webprogram/Paper140641.html

2. Cho SF, Anderson KC, Tai YT. Targeting B cell maturation antigen (BCMA) in multiple myeloma: potential uses of BCMA-based immunotherapy. Front Immunol. 2019;9:1821. doi:10.3389/fimmu.2018.01821

3. AlloCAR T Therapy. Allogene Therapeutics. Accessed December 5, 2020. https://www.allogene.com/allocar-t-therapy

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ALLO-715, Off-the-Shelf CAR T-Cell Therapy, Produces Early Promise in Multiple Myeloma - Cancer Network

Rocket Pharmaceuticals Presents Positive Clinical Data from its Fanconi Anemia and Leukocyte Adhesion Deficiency-I Programs at the 62nd American…

By adminDecember 8, 2020Stem Cell Medical Center

NEW YORK--(BUSINESS WIRE)--Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) (Rocket), a clinical-stage company advancing an integrated and sustainable pipeline of genetic therapies for rare childhood disorders, today presents updated interim data from its Fanconi Anemia (FA) and Leukocyte Adhesion Deficiency-I (LAD-I) programs at the 62nd American Society of Hematology (ASH) Annual Meeting. The data are highlighted in two oral presentations.

We are highly pleased with the data presented at ASH demonstrating ongoing evidence of efficacy and durability using Process B in both FA and LAD-I as we move towards potential registration, said Gaurav Shah, M.D., Chief Executive Officer and President of Rocket. Follow-up data from the Phase 1 and 2 trials for FA continue to support RP-L102 as a potential hematologic treatment option in the absence of cytotoxic conditioning. In five of the seven patients treated as of October 2020, there was evidence of engraftment. In addition, stabilization of peripheral blood counts in two of the three patients with at least 12-month follow-up, which declined substantially in these patients prior to gene therapy, suggests a halt in bone marrow failure progression. We look forward to reporting longer-term follow-up on these patients in the first half of 2021.

Dr. Shah continued, Additionally, we continue to see encouraging evidence of efficacy for RP-L201 for the treatment of LAD-I. Patients have shown sustained CD18 expression of 23% to 40%, far exceeding the 4-10% threshold associated with survival into adulthood. These data, on top of our exciting results from our lentiviral program for PKD, show our steady progress across three of our five gene therapy programs. We are proud of this progress and are committed to advancing our investigational gene therapies through development for patients and families facing these devastating disorders.

Key findings and details for each presentation are highlighted below. To access the presentations at the conclusion of the oral presentation, please visit: https://www.rocketpharma.com/ash-presentations/

Gene Therapy for Fanconi Anemia, Complementation Group A: Updated Results from Ongoing Global Clinical Studies of RP-L102 The data presented in the oral presentation are from seven of the nine patients treated as of the cutoff date of October 2020 in both the U.S. Phase 1 and global Phase 2 studies of RP-L102 for FA. Seven patients had follow-up data of at least 2-months, and three of the seven patients had been followed for 12-months or longer. Key highlights from the presentation include:

Presentation Details: Title: Gene Therapy for Fanconi Anemia, Complementation Group A: Updated Results from Ongoing Global Clinical Studies of RP-L102 Session Title: Gene Editing, Therapy and Transfer I Presenter: Agnieszka Czechowicz, M.D., Ph.D., Assistant Professor of Pediatrics, Division of Stem Cell Transplantation, Stanford University School of Medicine Session Date: Monday, December 7, 2020 Session Time: 11:30 a.m. - 1:00 p.m. (Pacific Time) Presentation Time: 12:15 p.m. (Pacific Time)

Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I): Results from Phase 1 The data presented in the oral presentation are from three pediatric patients with severe LAD-I, as defined by CD18 expression of less than 2%. The patients were treated with RP-L201, Rockets ex-vivo lentiviral gene therapy candidate. Patient L201-003-1001 was 9-years of age at enrollment and had been followed for 12-months as of a cutoff date of November 2020. Patient L201-003-1004 was 3-years of age at enrollment and had been followed for over 6-months. Patient L201-003-2006 was 7-months of age at enrollment and was recently treated with RP-L201. Key highlights from the presentation include:

Rockets LAD-I research is made possible by a grant from the California Institute for Regenerative Medicine (Grant Number CLIN2-11480). The contents of this press release are solely the responsibility of Rocket and do not necessarily represent the official views of CIRM or any other agency of the State of California.

Presentation Details: Title: Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I): Results from Phase 1 Session Title: Gene Editing, Therapy and Transfer I Presenter: Donald Kohn, M.D., Professor of Microbiology, Immunology and Molecular Genetics, Pediatrics (Hematology/Oncology), Molecular and Medical Pharmacology, and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles Session Date: Monday, December 7, 2020 Session Time: 11:30 a.m. - 1:00 p.m. (Pacific Time) Presentation Time: 12:30 p.m. (Pacific Time)

Conference Call Details Rocket management will host a conference call and webcast today December 7, at 6:00 p.m. EST. To access the call and webcast, please click here. The webcast replay will be available on the Rocket website following the completion of the call.

Investors may listen to the call by dialing (866) 866-1333 from locations in the United States or +1 (404) 260-1421 from outside the United States. Please refer to conference ID number 50038102

About Fanconi Anemia Fanconi Anemia (FA) is a rare pediatric disease characterized by bone marrow failure, malformations and cancer predisposition. The primary cause of death among patients with FA is bone marrow failure, which typically occurs during the first decade of life. Allogeneic hematopoietic stem cell transplantation (HSCT), when available, corrects the hematologic component of FA, but requires myeloablative conditioning. Graft-versus-host disease, a known complication of allogeneic HSCT, is associated with an increased risk of solid tumors, mainly squamous cell carcinomas of the head and neck region. Approximately 60-70% of patients with FA have a Fanconi Anemia complementation group A (FANCA) gene mutation, which encodes for a protein essential for DNA repair. Mutation in the FANCA gene leads to chromosomal breakage and increased sensitivity to oxidative and environmental stress. Increased sensitivity to DNA-alkylating agents such as mitomycin-C (MMC) or diepoxybutane (DEB) is a gold standard test for FA diagnosis. Somatic mosaicism occurs when there is a spontaneous correction of the mutated gene that can lead to stabilization or correction of a FA patients blood counts in the absence of any administered therapy. Somatic mosaicism, often referred to as natural gene therapy provides a strong rationale for the development of FA gene therapy because of the selective growth advantage of gene-corrected hematopoietic stem cells over FA cells.

About Leukocyte Adhesion Deficiency-I Severe Leukocyte Adhesion Deficiency-I (LAD-I) is a rare, autosomal recessive pediatric disease caused by mutations in the ITGB2 gene encoding for the beta-2 integrin component CD18. CD18 is a key protein that facilitates leukocyte adhesion and extravasation from blood vessels to combat infections. As a result, children with severe LAD-I are often affected immediately after birth. During infancy, they suffer from recurrent life-threatening bacterial and fungal infections that respond poorly to antibiotics and require frequent hospitalizations. Children who survive infancy experience recurrent severe infections including pneumonia, gingival ulcers, necrotic skin ulcers, and septicemia. Without a successful bone marrow transplant, mortality in patients with severe LAD-I is 60-75% prior to the age of 2 and survival beyond the age of 5 is uncommon. There is a high unmet medical need for patients with severe LAD-I.

About Rocket Pharmaceuticals, Inc. Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) (Rocket) is advancing an integrated and sustainable pipeline of genetic therapies that correct the root cause of complex and rare childhood disorders. The companys platform-agnostic approach enables it to design the best therapy for each indication, creating potentially transformative options for patients afflicted with rare genetic diseases. Rocket's clinical programs using lentiviral vector (LVV)-based gene therapy are for the treatment of Fanconi Anemia (FA), a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, Pyruvate Kinase Deficiency (PKD) a rare, monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia and Infantile Malignant Osteopetrosis (IMO), a bone marrow-derived disorder. Rockets first clinical program using adeno-associated virus (AAV)-based gene therapy is for Danon disease, a devastating, pediatric heart failure condition. For more information about Rocket, please visit http://www.rocketpharma.com.

Rocket Cautionary Statement Regarding Forward-Looking Statements Various statements in this release concerning Rocket's future expectations, plans and prospects, including without limitation, Rocket's expectations regarding its guidance for 2020 in light of COVID-19, the safety, effectiveness and timing of product candidates that Rocket may develop, to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Infantile Malignant Osteopetrosis (IMO) and Danon Disease, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as "believe," "expect," "anticipate," "intend," "plan," "will give," "estimate," "seek," "will," "may," "suggest" or similar terms, variations of such terms or the negative of those terms. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket's ability to monitor the impact of COVID-19 on its business operations and take steps to ensure the safety of patients, families and employees, the interest from patients and families for participation in each of Rockets ongoing trials, our expectations regarding the delays and impact of COVID-19 on clinical sites, patient enrollment, trial timelines and data readouts, our expectations regarding our drug supply for our ongoing and anticipated trials, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, Rocket's dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the section entitled "Risk Factors" in Rocket's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, filed November 6, 2020 with the SEC. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

Negrin Shines Light on the Orca-T Story in GVHD – OncLive

By adminDecember 8, 2020Stem Cell Medical Center

What started out as a journey to better understand regulatory T cells has now led to an intriguing approach with an investigational cell therapy designed to prevent the risk of graft-versus-host disease (GVHD) and to improve relapse-free survival rates in patients undergoing hematopoietic stem cell transplantation (HSCT).

Data of a phase 1/2 trial recently showed that the first-generation precision cell treatment Orca-T compared with a historical control of standard HSCT demonstrated faster neutrophil (median, 12 days vs 14 days; P < .0001) and platelet engraftment (median, 11 days vs 17 days; P < .0001), decreased incidence of grade 2 or higher GVHD at 100 days (10% vs 30%, P = .005) and chronic GVHD at 1 year (3% vs 46%, P = .0002).1,2

The 1-year GVHD-free and GVHD relapse-free survival (GRFS) rates were 75% with the use of Orca-T vs 31% with standard HSCT (P < .0001). The comparator cohort was derived from contemporaneous patients who had been treated at Stanford University with a conventional allograft.

Along with feasibility of the approach, the results also highlight how Orca-T demonstrates potent anti-leukemic activity in patients who have active disease at HSCT, which suggests that the decrease of GVHD does not impact graft-vs-leukemia (GvL).

That is the most exciting part about the Orca-T story; it is the ability to do this with precision, with speed, and to export it to other sites. The results are intriguing, and very supportive, said Robert Negrin, a professor of medicine (blood and marrow transplantation), and chief of the Division of Blood and Marrow Transplantation at Stanford University.

In an interview with OncLive, Negrin, who is senior author on the trial, shared the evolution of Orca-T as a novel approach to HSCT, highlighted his robust experience with using this cell therapy at Stanford University, and how Orca-T is a potential prevention method for GVHD.

OncLive: Please provide some background to this therapeutic approach. What is the mechanism of action? How is it effective in patients undergoing transplant?

Negrin: This whole idea came from mouse studies many, many years ago, where we identified GVHD as being a dysregulated immune reaction that just keeps going, and going, and going. Like you and I, when we react to something, we have a reactionlet's say, influenza. Our body responds, and then we stop reacting and you get better. With GVHD, what we noticed in using a bioluminescent animal model is that the alloreactive T cells just keep going, going, and going and are unrelenting in mice, just like in people. The problem is very similar and affects certain organs in a very similar way.

Therefore, we went about trying to understand the use of so-called regulatory cells. These are cells that everybody has that help control immune reactions. We just applied them in this clinical scenario, first in mice work done by Matthias Edinger, MD, when he was a postdoctoral fellow many years ago [and other researchers]. All of them were very actively involved in these studies, and showed, somewhat surprisingly, that the administration of regulatory T cells could control this dysregulated immune response that we called GVHD.

Probably more surprising was that, at least in the animal models, it also allowed for the benefits of transplant, namely, the graft-vs-tumor effect and better immune recovery. This was in large part because GVHD also impacts the immune repertoire and where the immunity is developed in the recipient.

All of this was very nice in mouse models and was very elegant. We did a lot of studies, published a number of nice papers, and thought this would be a great idea because it sort of solved, or at least addressed, the principal problems after bone marrow transplantationnamely, avoidance of GVHD yet retention of graft-versus-tumor effects and better immunity. A lot of times, people say, "Oh, that sounds good in mice, but, that's too good to be true." And, theyll ask, "Will that all work in people?"

Where did the biggest challenges lie in this approach?

The big challenge came about to try to apply this to patients. We also have one other interesting point that is relevant. If we gave the regulatory T cells first, before the so-called conventional CD4+/CD8+ cells, that allowed for a lower dose of regulatory T cells. This is because a big challenge is the paucity of these cells; you and I don't have that many.

Then, the other big challenge was the technical ability to isolate in cells. What we do in mice is cell sorting, which is a standard technology. But, that was not developed in people because we're bigthere are a lot of cells, and cell sorting is rather slow, and it's very specific. To get enough cells takes a really long time. It's somewhat of a heroic thing to do in people, to get the adequate amount ourselves; of course, we don't really know what this proper cell dose is.

However, what we thought we learned was that the ratio of conventional to regulatory T cells was the key component. Also, if you give the regulatory T cells first, you can get fewer numbers. Those are things you can do in transplant. You can get the cell from the donor, and you can give cells in a certain sequence; all of those things are very doable. It seemed like an attractive thing to do in patients.

Then, the question was: Does it work? There are 3 groups that have really pioneered this work. The first study came from the University of Perugia in Italy. They did this in haploidentical transplantation; you cannot avoid immunosuppression in haploidentical transplants. They were able to show in several nice papers that you could do this strategy, and seemingly, get away with low risk of GVHD, and also low relapse. This is because the other issue is: how do you measure the graft-vs-tumor effect? There is no assay, and we have no test; you have to wait and see who relapses and who doesn't. Therefore, they also showed rather convincingly that you could reduce GVHD risk, yet, there was a very low risk of relapse in their high-risk patient population. Those were very important [data].

Another study from the University of Minnesota did this with umbilical cord blood. They expanded the regulatory T cells from a third cord blood unit, which is somewhat heroicit is another level of complexity to isolate the cells and then expand them. We did this in matched donorseither matched siblings or matched unrelated donors. We published a paper in JCI Insight several years ago showing the initial results, and they look quite favorable.

Therefore, what I think is most exciting about what Orca Bio has done is they are developing technology to isolate the cells more quickly, to be able to do this on a clinical scale, with precision, and with speed. Also, [they are developing the technology] to be able to distribute it to anybody, because the criticism of all these studies is that, "Oh, that's nice. But, this is a single-institution study. Is this really true? Can this be exported? Could this be something that [an organization] other than these [individual] centers are really focused in this area and have developed these technologies could really do? Orca Bio is developing the technology, and improving the technology, because it's still very cumbersome, and exporting the technology so that you could do this, theoretically, at any center.

That's what I think is most exciting about the Orca Bio abstract; it is demonstrating that this can be done. It certainly opens the door to prevention of GVHD. As we move into an era of using cell-based therapeutics, now, this opens up many other possibilities, because you use these regulatory cells and autoimmune disorders and organ transplant tolerance. There are many other cell types that have potential clinical utility, but getting them, and purifying them, is a big challenge. There are many other possibilities that one could think of.

Obviously, more time will be required to follow these patients, but they certainly are supportive of the idea that you can improve overall outcomes using this strategy. That's what we hope to be able to demonstrate further.

Please focus on the scalability of this approach. Through these types of collaborations, how do you see Orca-T potentially moving through the FDA pipeline?

In academia, we don't develop drugs. It's too much, we don't have the resources, we don't have the capability, and we don't have the monitoring capability that is required for multi-institutional studies. Where these commercial partners come in is, they can raise money for interesting concepts, which Orca Bio has done, and they can export this to other centers, and that's critically important.

As we've seen in the CAR T-cell [therapy] world, that can be a quite successful commercial business. Also going through the process of an FDA approvalwhich Orca Bio is moving along in that processand getting the right designations is critically important to commercial entities. In academia, it's important to us, but that's just not our focus.

We don't have the resources around, the people and the expertise to really drive things through that process. We're good at developing the studies and getting FDA approvals, and [investigational new drug applications], but not really [good at] developing drugs as a commercial entity. This collaboration is key to doing this successfully; for example, at Orca Bio, [they have] technology to separate cells more efficiently and effectively. They also have the resources to do a multi-institutional clinical trial, and the expertise to move something through and present it to the FDA. Those are key components.

Could you expand on the study and respective data from this phase 1/2 trial?

Here at Stanford Cancer Institute, we did find in our patients that giving low doses of immunosuppressive medications with a single agent seem to improve the outcomes, and it's remarkable how well these patients have gone through the transplant. It's a little bit hard to appreciate an abstract until you take care of these patients, and many of them just sort of move to the transplant with relatively little challenges. We have not seen greater risks of things like infection [or] disease recurrence; those are obviously things that will be followed.

When we look at the 1-year GVHD relapse-free survival rate, which is an endpoint that most transplant studies would agree is the most important end point, the overall outcomes are much more favorable compared with a historical control group.

The data are very encouraging, and the overall outcomes look very strong in a reasonable number of patients now. We think it's important for the community to hear about it, and to get it on everybody's radar, and be excited about trying to move this forward as a more standard therapy. This is still a clinical trial, so it's not, it's not part of any standard therapies yet. We are using this quite regularly and have been very encouraged by the ease of which patients go through the transplant. It's still an allogeneic transplant; there still are many challenges there. However, these patients seem to be doing quite well, we're very encouraged, and so we keep going.

How does this approach impact patient outcomes as it relates to quality of life (QoL)?

The hard end points of 1-year relapse-free survival is obviously the most important to patients. However, going through an allogeneic transplant is obviously an incredibly difficult thing. Fortunately, I've only seen it [from] the doctor side, not [as a] patient.

However, I've seen many, many patients, and the quality of their life as they go through this experience is very important to all of us. As we saw these patients go through these studies, we felt like we were capturing something that was really important, and that is the ease [at which] many patients went through this experience, which just seemed different. It's hard to capture that.

It's really important for patients to speak and, and the way patients speak is in different ways. One way is through the QoL measures that they answer. This is [what they find] important, this is what they experiencednot what we say is happening. That's really important to hear that voice too. Those are data we're trying to collect. It's not so easy, because going through a bone marrow transplant is a poor QoL for everybody. But, by just to trying to capture this, [Orca-T seems] better than what we what we thought.

How has this changed the mindset of cell-based approaches in the community?

What has changed is the belief in the concept of cell-based therapies. A lot of these things are somewhat fanciful. It is also important to show that we can translate from an animal model [to a human]. There is a lot of criticism of animal modeling, because people say, "Well, it's nice for animal models, but it doesn't really translate into the clinic." Actually, my view is that because we don't actually follow the animal models, there are many compromises one needs to make. When you translate studies from animals to humans, there are many differences, and it's really important to try to follow them as carefully as you can within the limitations of what is possible. We were very engaged in that and tried to follow as carefully as we could. To me, that is very encouragingthat you can study things in animals that generate new concepts and be able to translate that into a clinical trial.

Obviously, with all of the caveats of an early-phase clinical trial, more time needs to pass, more patients to be treated, and you need to export [the treatment] to other centers. That's a really important point, because there are many things that get lost because, "it's too complicated. It's too expensive. People can't do it." I don't think anybody can do high-speed cell sorting, as a clinical project in a standard or standard cell-processing laboratory. It's above the level of what most processing laboratories can do.

References

Link:
Negrin Shines Light on the Orca-T Story in GVHD - OncLive

BeiGene Announces the Approval in China of BLINCYTO (Blinatumomab) for Injection for Adult Patients with Relapsed or Refractory B-Cell Precursor Acute…

By adminDecember 8, 2020Stem Cell Medical Center

BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)--BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biotechnology company focused on developing and commercializing innovative medicines worldwide, today announced that the China National Medical Products Administration (NMPA) has approved BLINCYTO (blinatumomab) for injection for the treatment of adult patients with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). The biologics license application (BLA) had been submitted by Amgen and received priority review by the Center for Drug Evaluation (CDE) of the NMPA. Developed by Amgen and licensed to BeiGene in China under a strategic collaboration commenced earlier this year, this is the first approval for BLINCYTO in China and BeiGenes first product licensed from Amgen to be newly approved. With this approval, BLINCYTO has become the first bispecific immunotherapy approved in China.

This approval of BLINCYTO provides us with an opportunity to offer adult patients in China with relapsed or refractory B-cell precursor ALL the first approved immunotherapy treatment for their disease. BLINCYTO is the first immunotherapy to demonstrate superior overall survival versus chemotherapy, more than doubling patients chances for survival, when used in first salvage R/R ALL in studies outside of China, commented Xiaobin Wu, Ph.D., General Manager of China and President of BeiGene. We are working to ensure BLINCYTO is available to patients in China as soon as possible. Our commercial organization of more than 1,500 people in China is excited to add BLINCYTO to our product portfolio, which now includes six approved cancer treatments.

The approval of BLINCYTO was based on results from the Phase 3 trial (NCT03476239) in China evaluating the efficacy and safety of BLINCYTO in adult patients with Philadelphia-negative R/R B-cell precursor ALL. Results of the interim analysis of 67 patients showed that the efficacy results in Chinese subjects were generally consistent with those in the global and Japan studies in subjects with Philadelphia-negative R/R ALL. The complete response/complete response with partial recovery of blood cells (CR/CRh) rate within two cycles of BLINCYTO treatment (the primary endpoint) was 47.8% (32 of 67 subjects; 95% CI: 35.4, 60.3). The median overall survival time was 9.6 months (95% CI: 6.4, not estimable). The safety profile observed for Chinese subjects in this study was consistent with that observed in the global studies evaluating BLINCYTO in R/R ALL. No new safety risks were identified based on these interim analyses of adverse events in Chinese subjects.

Our collaboration with BeiGene is advancing Amgens oncology pipeline for patients with significant unmet medical needs. We are confident the approval of BLINCYTO in China has the potential to make a meaningful difference to adult patients with R/R B-cell precursor acute lymphoblastic leukemia, said My Linh Kha, Vice President & General Manager, Amgen Japan Asia-Pacific (JAPAC). We are deeply committed to continuing to bring therapeutic options to treat debilitating cancers for patients in China, while also actively supporting the Governments focus on healthy aging through innovative products and initiatives designed to prevent chronic diseases, such as cardiovascular disease and fragility fracture.

About Acute Lymphoblastic Leukemia (ALL)

Acute lymphoblastic leukemia (ALL), also known as acute lymphocytic leukemia, is a rapidly progressing cancer of the blood and bone marrow that occurs in both adults and children1. ALL accounts for approximately 20% of all adult leukemia, and in China there were an estimated 82,607 new cases of leukemia in 20182,3. In children, the relapse rate of ALL is nearly 10%, while in adults the relapse rate is closer to 50%4.

About BLINCYTO (blinatumomab)

BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE) immuno-oncology molecule that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

BiTE molecules are a type of immuno-oncology therapy being investigated for fighting cancer by helping the body's immune system to detect and target malignant cells. The modified molecules are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE immuno-oncology molecules help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE immuno-oncology therapies are currently being investigated for their potential to treat a wide variety of cancers.

BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration and is approved in the U.S. for the treatment of:

In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of:

In China, BLINCYTO is indicated for the treatment of adult patients with relapsed or refractory B-cell precursor ALL.

Important U.S. Safety Information

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

Contraindications

BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

Adverse Reactions

Dosage and Administration Guidelines

Please see full Prescribing Information and medication guide for BLINCYTO at http://www.BLINCYTO.com.

About BeiGene

BeiGene is a global, commercial-stage biotechnology company focused on discovering, developing, manufacturing, and commercializing innovative medicines to improve treatment outcomes and access for patients worldwide. Our 4,700+ employees in China, the United States, Australia, Europe, and elsewhere are committed to expediting the development of a diverse pipeline of novel therapeutics. We currently market two internally discovered oncology products: BTK inhibitor BRUKINSA (zanubrutinib) in the United States and China, and anti-PD-1 antibody tislelizumab in China. We also market or plan to market in China additional oncology products licensed from Amgen Inc., Celgene Logistics Srl, a Bristol Myers Squibb (BMS) company, and EUSA Pharma. To learn more about BeiGene, please visit http://www.beigene.com and follow us on Twitter at @BeiGeneUSA.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the commercialization and potential benefits of BLINCYTO; and BeiGenes plans and expectations for the commercialization of its and Amgens other oncology products and pipeline assets. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed products and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its technology and drugs; BeiGene's reliance on third parties to conduct drug development, manufacturing and other services; BeiGenes limited operating history and BeiGene's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates; the impact of the COVID-19 pandemic on the Companys clinical development, commercial and other operations, as well as those risks more fully discussed in the section entitled Risk Factors in BeiGenes most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law.

BLINCYTO and BiTE are registered trademarks of Amgen Inc.

1 Mayo Clinic. Acute lymphocytic leukemia. https://www.mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/symptoms-causes/syc-20369077

2 Baljevic M, Jabbour E, O'Brien S, Kantarjian HM (2016). "Acute Lymphoblastic Leukemia".

3 Global Cancer Observatory. https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf

4 Leukaemia Care. Relapse in Acute Lymphoblastic Leukaemia (ALL). https://media.leukaemiacare.org.uk/wp-content/uploads/Relapse-in-Acute-Lymphoblastic-Leukaemia-ALL-Web-Version.pdf

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BeiGene Announces the Approval in China of BLINCYTO (Blinatumomab) for Injection for Adult Patients with Relapsed or Refractory B-Cell Precursor Acute...

Preliminary Results from NexImmune’s Phase 1/2 Trial of NEXI-001 in AML Presented at 62nd ASH Annual Meeting and Exposition – GlobeNewswire

By adminDecember 8, 2020Stem Cell Medical Center

December 07, 2020 17:31 ET | Source: NexImmune, Inc.

GAITHERSBURG, Md., Dec. 07, 2020 (GLOBE NEWSWIRE) -- NexImmune, a clinical-stage biotechnology company developing a novel approach to immunotherapy designed to employ the bodys own T cells to generate a specific, potent and durable immune response that mimics natural biology, today announced that City of Hopes Monzr Al Malki, M.D., delivered an oral presentation at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition featuring initial data from the Phase 1/2 trial of NEXI-001 in AML. Entitled Preliminary Results of the First-in-Human Study of NEXI-001, a Multi-Antigen Specific CD8+ T Cell Product, in Acute Myeloid Leukemia (AML) Patients with Relapsed Disease after Allogeneic Hematopoietic Cell Transplantation (Allo-HSCT) Demonstrate Early Signs of Safety, Tolerability and Robust Immune Responses, the presentation included responses following a single infusion of the experimental therapy.

These data represent safety and tolerability results from the first five patients treated and reflect a median of four months of follow-up with infusion doses ranging from 50-200 million total T cells. As noted by Dr. Al Malki in his presentation, there have been no cases of acute Graft versus Host Disease (aGvHD), Cytokine Release Syndrome (CRS), immune cells-associated neurological syndromes (ICANs), or infusion related reactions (IRRs) reported to-date, nor have there been any treatment-related adverse events (AEs) observed.

Biomarker data characterizing initial immunologic responses for the first three patients analyzed were also shared. Absolute lymphocyte counts, or ALC, were followed over time after the administration of lymphodepleting therapy, and showed a rapid return to baseline levels for each patient assessed (range 3 to 35 days). In addition, data on T cell reconstitution after lymphodepletion demonstrated that a single infusion of NEXI-001 T cells triggered a broad, rapid and robust immune response, inclusive of both CD8+ and CD4+ T cell types. TCR analysis showed the presence, persistence, expansion and migration of individual NEXI-001 T cell clones from the peripheral blood to the bone marrow of each patient. Finally, the immune phenotype of individual T cell subtypes in each NEXI-001 product were maintained in the peripheral blood of each patient at all time points measured, up to two months. These included sustained populations of T stem-cell-like memory and T central memory subtypes.

Early results from this Phase 1/2 trial suggest that infusion of the NEXI-001 product is well-tolerated and capable of triggering early, robust and persistent cell-mediated immune responses, said Dr. Al Malki, the trials lead investigator and associate clinical professor in City of Hopes Department of Hematology & Hematopoietic Cell Transplantation. The initial data are encouraging, and we look forward to dosing more patients with longer follow-up in order to more fully characterize the clinical potential of this exciting new cell therapy.

Relapse after allo-HSCT is the leading cause of death in patients with AML and represents a significant challenge for treating physicians. There are no approved therapies, and current treatment options are limited. Donor lymphocyte infusions (DLIs) represent the current standard of care but are associated with modest Graft versus Leukemia (GvL) responses and high rates of life-threatening GvHD-associated toxicities. There is significant need for new cellular therapies with potential to enhance the benefits of GvL while decreasing the incidence of GvHD-related toxicities.

Han Myint, M.D., Chief Medical Officer at NexImmune, added, While still early in this trial, we believe the initial data reported, combined with the unique and consistent composition of each NEXI-001 product, may offer a cell therapy with potential to decouple the benefits of GvL from the toxicities associated with GvHD, which would be transformative for both allogeneic stem cell transplant patients and the physicians that provide care for them.

About the Phase 1/2 NEXI-001 Clinical Trial The first clinical trial with NEXI-001 is a prospective, multi-center, open-label, single-arm, dose-escalating Phase 1/2 study that aims to enroll between 22 to 28 patients. The primary objective is to assess the safety and tolerability of a single infusion of NEXI-001 T cells in patients with AML who have either minimum residual disease (MRD) or relapsed disease after a human leukocyte antigen (HLA)-matched allo-HSCT. Secondary objectives include signals of immunologic responses and preliminary anti-tumor activity. Additional analysis will assess the in vivo persistence, proliferation, functionality and TCR repertoire of NEXI-001 T cells as measured in blood and bone marrow samples.

This study includes two phases. The initial Safety Evaluation Phase determines the safety and tolerability of a single infusion of NEXI-001 at escalating dose levels. In the second part of the study, the Dose Expansion Phase, investigators further define safety and will also evaluate the initial efficacy of NEXI-001 T cells at the dose established in the Safety Evaluation Phase. Once a Recommended Phase II Dose has been determined, safety, tolerability and initial clinical response will become the objectives of the expansion phase of the trial, which is expected to begin in [the first quarter] of 2021.

NEXI-001 products contain populations of CD8+ T cells directed against HLA 02.01-restricted peptides from the WT1, PRAME and Cyclin A1 antigens, each of which is commonly over-expressed on AML blasts and leukemic stem cells. Each NEXI-001 product is composed of T cell memory subtypes that combine anti-tumor potency with long-term persistence. Of significance to this Phase 1/2 trial, each patient-specific experimental cell therapy product also contains very low proportions of T cell subtypes with potential to cause GvHD-related toxicities.

About NexImmune NexImmune is a clinical-stage biotechnology company developing unique approaches to T cell immunotherapies based on its proprietary Artificial Immune Modulation (AIM) technology. The AIM technology is designed to generate a targeted T cell-mediated immune response and is initially being developed as a cell therapy for the treatment of hematologic malignancies. AIM nanoparticles act as synthetic dendritic cells to deliver immune-specific signals to targeted T cells and can direct the activation or suppression of cell-mediated immunity. In cancer, AIM-expanded T cells have demonstrated best-in-class anti-tumor properties as characterized by in vitro analysis, including a unique combination of anti-tumor potency, antigen target-specific killing, and long-term T cell persistence. The modular design of the AIM platform enables rapid expansion across multiple therapeutic areas, with both cell therapy and injectable products.

NexImmunes two lead T cell therapy programs, NEXI-001 and NEXI-002, are in Phase 1/2 clinical trials for the treatment of relapsed AML after allo-HSCT and multiple myeloma refractory to at least three prior lines of therapy, respectively. The Companys pipeline also has additional preclinical programs, including cell therapy and injectable product candidates for the treatment of solid tumors, autoimmune disorders and infectious diseases.

For more information, visit http://www.neximmune.com.

Media Contact: Mike Beyer Sam Brown Inc. Healthcare Communications 312-961-2502 mikebeyer@sambrown.com

Investor Contact: Chad Rubin Solebury Trout +1-646-378-2947 crubin@soleburytrout.com

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Preliminary Results from NexImmune's Phase 1/2 Trial of NEXI-001 in AML Presented at 62nd ASH Annual Meeting and Exposition - GlobeNewswire

Sutro Biopharma Presents Data from Ongoing Phase 1 Dose-Escalation Study for STRO-001 for the Treatment of B-cell Non-Hodgkin Lymphoma at the 62nd…

By adminDecember 8, 2020Stem Cell Medical Center

SOUTH SAN FRANCISCO, Calif., Dec. 7, 2020 /PRNewswire/ -- Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation cancer and autoimmune therapeutics, today announced a poster presentation at the virtual 62nd American Society of Hematology (ASH) Annual Meeting for the ongoing Phase 1 dose-escalation clinical trial for its CD74-targeted antibody drug conjugate (ADC) STRO-001 for patients with late-line Non-Hodgkin Lymphoma (NHL). Additionally, data were presented from preclinical studies conducted in collaboration with researchers from the Fred Hutchinson Cancer Research Center.

"With three product candidates in the pipeline actively enrolling patientsSTRO-001, STRO-002, our folate receptor alpha- (FolR) targeting ADC, and CC-99712 in partnership with Bristol Myers Squibb, a BCMA-targeting ADCSutro is working on addressing unmet needs via targeted therapies that can tackle cancer evolution," said Bill Newell, Sutro's Chief Executive Officer. "The encouraging safety and preliminary efficacy clinical data presented at ASH on STRO-001 for the treatment of late-line NHL further validates our platform and unique approach to ADC design, creating potential first-in-class and/or best-in-class therapeutic candidates."

STRO-001 Phase 1 Dose Escalation Interim DataSTRO-001-BCM1 is an ongoing first-in-human, phase 1 dose-escalation study evaluating the safety, tolerability, and preliminary antitumor activity of STRO-001 in adults with B-cell malignancies. The study is ongoing, and data presented at ASH included results from the NHL cohort. There were 21 NHL patients treated and 18 evaluable patients for response. Patients had a median of 5 prior therapies. 6/21 patients (29%) had previous stem cell transplant or CAR-T therapy. Data as of October 30, 2020 are as follows:

"These results continue to demonstrate the potential clinical benefit of STRO-001 treatment in patients with NHL who are heavily pretreated, with a median of five prior lines of treatment," said Dr. Arturo Molina, Sutro's Chief Medical Officer. "We are especially pleased for the patients who responded to STRO-001 after previously progressing on CAR-T treatments and an additional post- CAR-T regimen to which they had no response, seeing comparable duration of disease control to the duration on a cell therapy. STRO-001 has been well tolerated. We look forward to continuing the dose-escalation study to learn more about the potential for STRO-001 for patients with NHL."

Maximum tolerated dose (MTD) was not reached at 2.5 mg/kg. Active enrollment in the NHL cohort continues at the 3.5 mg/kg dose level and additional higher dose levels may be explored. The trial, registered with clinicaltrials.gov identifier NCT03424603, continues to enroll patients in dose escalation in both multiple myeloma (MM) and NHL cohorts.

The virtual poster titled "Preliminary Results of an Ongoing Phase 1 Dose Escalation Study of the Novel Anti-CD74 Antibody Drug Conjugate (ADC), STRO-001, in Patients with B-cell Non-Hodgkin Lymphoma," presented by Nirav N. Shah, M.D., Associate Professor of Medicine at Medical College of Wisconsin, is accessible through the Clinical/Scientific Presentation and Publication Highlights page of the News section of the company's website atwww.sutrobio.com.

Preclinical Data from Fred Hutchinson Cancer Research Center in Collaboration with SutroFred Hutchinson Cancer Research Center, in collaboration with Sutro, presented preclinical models showing the potential of CD74-targeted therapies, and in particular STRO-001, for the treatment of acute myelogenous leukemia (AML). The research is out of the lab of Soheil Meshinchi, M.D., Ph.D., Professor, Clinical Research Division at Fred Hutchinson Cancer Center and Professor of Pediatrics at University of Washington School of Medicine.

"My team at Fred Hutchinson Cancer Research Centerhas built arobustcomputational platform leveraging our large AML transcriptome dataset to identify highly expressedantigens on leukemic cells that are being targetedby agentsin early phase trials or preclinical developmentwith the goal ofrepurposing these therapeuticsfor use in AML,"said Soheil Meshinchi, M.D., Ph.D."One of these therapies wastheSTRO-001 ADC which targets the cell surface protein CD74. We have demonstrated that CD74 is highly expressed in a significant proportion of patients with AML. Our initial studies of STRO-001 ADC in AML cell lines demonstratedrobustinvitro cytotoxicity on AML cell lines expressing high-to moderate-levels of CD74, with no cytotoxicity in cells with no CD74 expression. This in vitro data, which identifies CD74 as a viable target in AML, coupled with the 27% incidence of CD74 in nearly 1,000 pediatric AML patients from our clinical trial with bortezomib, strengthens the notion that targeting CD74 with STRO-001 represents a viable targeted therapy in this patient population. In addition to AML, CD74 is highly expressed in high risk acute lymphoblastic leukemia (ALL), including Ph-positive and Ph-like ALL, thus providing rationale for exploring the efficacy of STRO-001 inall leukemias.

About Sutro Biopharma

Sutro Biopharma, Inc., located in South San Francisco, isa clinical-stage drug discovery, developmentand manufacturing company. Using precise protein engineering and rational design, Sutro is advancing next-generation oncology therapeutics.

Sutro's proprietary and integrated cell-free protein synthesis platform XpressCF and site-specific conjugation platform XpressCF+ led to the discovery of STRO-001 and STRO-002, Sutro's first two internally-developed ADCs. STRO-001 is a CD74-targeting ADC currently being investigated in a Phase 1 clinical trial of patients with advanced B-cell malignancies, including multiple myeloma and non-Hodgkin lymphoma. STRO-001 was granted Orphan Drug Designation by the FDA for multiple myeloma in October 2018. STRO-002 is a folate receptor alpha (FolR)-targeting ADC, currently being investigated in a Phase 1 clinical trial of patients with ovarian and endometrial cancers. This is the second product candidate to be evaluated in clinical trials resulting from Sutro's XpressCF and XpressCF+ technology platforms. A third program, CC-99712 (BCMA-targeting ADC), which is part of Sutro's collaboration with Bristol Myers Squibb (formerly Celgene Corporation), is enrolling patients for its Phase 1 clinical trial of patients with multiple myeloma. Sutro's proprietary technology was responsible for the discovery and manufacturing of CC-99712, for which Bristol Myers Squibb has worldwide development and commercialization rights. Sutro is entitled to development and regulatory milestone payments and tiered royalties from Bristol Myers Squibb for this BCMA ADC. Sutro is dedicated to transforming the lives of cancer patients by creating medicines with improved therapeutic profiles for areas of unmet need.

To date, Sutro's platform has led to cytokine-based immuno-oncology therapies, ADCs, vaccines and bispecific antibodies directed at precedented targets in clinical indications where the current standard of care is suboptimal. The platform allows it to accelerate discovery and development of potential first-in-class and best-in-class molecules through rapid and systematic evaluation of protein structure-activity relationships to create optimized homogeneous product candidates.

In addition to developing its own oncology pipeline, Sutro is collaborating with select pharmaceutical and biotech companies to discover and develop novel,next-generation therapeutics. As the pace of clinical development accelerates, Sutro and its partners are developing therapeutics designed to more efficiently kill tumors without harming healthy cells.

Additional multimedia content from Sutro regarding STRO-001 and STRO-002 can be foundhereandhere.

Follow Sutro on Twitter,@Sutrobio, and atwww.sutrobio.comto learn more about our passion for changing the future of oncology.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, anticipated preclinical and clinical development activities, timing of clinical trials and announcements of clinical results, potential benefits of the company's product candidates and platform and potential market opportunities for the company's product candidates. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Although the company believes that the expectations reflected in such forward-looking statements are reasonable, the company cannot guarantee future events, results, actions, levels of activity, performance or achievements, and the timing and results of biotechnology development and potential regulatory approval is inherently uncertain. Forward-looking statements are subject to risks and uncertainties that may cause the company's actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to the company's ability to advance its product candidates, the receipt and timing of potential regulatory designations, approvals and commercialization of product candidates, the impact of the COVID-19 pandemic on the Company's business, clinical trial sites, supply chain and manufacturing facilities, the Company's ability to maintain and recognize the benefits of certain designations received by product candidates, the timing and results of preclinical studies and clinical trials, the company's ability to fund development activities and achieve development goals, the company's ability to protect intellectual property, and the Company's commercial collaborations with third parties and other risks and uncertainties described under the heading "Risk Factors" in documents the company files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and the company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof.

Investor Contact

Annie J. Chang Sutro Biopharma +1 650-255-8806 [emailprotected].com

Media ContactsDavid Schull Russo Partners (212) 845-4271 [emailprotected]

SOURCE Sutro Biopharma

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Treatment with Investigational LentiGlobin Gene Therapy for Sickle Cell Disease (bb1111) Results in Complete Elimination of SCD-Related Severe…

Anatomy of a vaccine: What it takes to create a safe, effective COVID shot – University of California

Magenta Therapeutics Announces Commencement of First Phase 2 Clinical Trial of MGTA-145 for Stem Cell Mobilization, Oral Presentation of MGTA-145…

Precigen Presents New Data Supporting the Safety, Clinical Activity, Expansion and Persistence of PRGN-3006 UltraCAR-T at the 62nd ASH Annual Meeting…

ALLO-715, Off-the-Shelf CAR T-Cell Therapy, Produces Early Promise in Multiple Myeloma – Cancer Network

Rocket Pharmaceuticals Presents Positive Clinical Data from its Fanconi Anemia and Leukocyte Adhesion Deficiency-I Programs at the 62nd American…

Negrin Shines Light on the Orca-T Story in GVHD – OncLive

BeiGene Announces the Approval in China of BLINCYTO (Blinatumomab) for Injection for Adult Patients with Relapsed or Refractory B-Cell Precursor Acute…

Preliminary Results from NexImmune’s Phase 1/2 Trial of NEXI-001 in AML Presented at 62nd ASH Annual Meeting and Exposition – GlobeNewswire

Sutro Biopharma Presents Data from Ongoing Phase 1 Dose-Escalation Study for STRO-001 for the Treatment of B-cell Non-Hodgkin Lymphoma at the 62nd…