Personalizing Therapies for Optimal Outcomes in Multiple Myeloma – Targeted Oncology

How clinicians choose to sequence treatment for patients with multiple myeloma to provide a more personalized approach has played an important role in managing this disease over time. According to Paul Richardson, MD, treating multiple myeloma is never a one-size-fits-all approach, so it is important to tailor treatments for each patient.

Multiple myeloma is a highly heterogeneous disease. It's full of multiple subgroups of patients. In that context, the ability to have rational combination strategies that integrate small molecule approaches, immune therapies, transplantation and so forth, is an absolutely vital way forward, said Richardson, Clinical Program Leader of the and Director of Clinical Research at the Jerome Lipper Multiple Myeloma Center, and institute physician at Dana-Farber Cancer Institute, as well as the RJ Corman professor of Medicine at Harvard Medical School, in an interview with Targeted OncologyTM.

When choosing between the available regimens for patients with multiple myeloma, experts look at the disease characteristics of patients, including stage, age, kidney function, response to prior therapies, and more, to create this more personalized approach and improve the quality-of-life of patients.

In the interview, Richardson highlighted his presentation from the 4th Annual Miami Cancer Institute Global Summit on Immunotherapies for Hematologic Malignancies on updates and personalization of treatments for patients with multiple myeloma.

Targeted Oncology: Can you discuss the importance of personalizing treatments for patients with multiple myeloma?

Richardson: It was my privilege to present this [topic] at the fourth meeting, led by Guenther Koehne, MD, PhD. It was an outstanding meeting and I'm very grateful to the organizers for inviting me. My remit was to frame the immune rationale or the immune therapy rationale in myeloma and contextualize it in the incredibly exciting environment we have with multiple treatment options for our patients, recognizing the promise of immune therapies, and at the same time, recognizing the value of backbone approaches that have continued to provide benefit.

The overarching thrust of my presentation was to share that this is never a case of one-size-fits-all, but rather all hands to the pump. We need all the tools that we're fortunate enough to have. Multiple myeloma is a highly heterogeneous disease. It's full of multiple subgroups of patients. In that context, the ability to have rational combination strategies that integrate small molecule approaches, immune therapies, transplantation and so forth, is an absolutely vital way forward.

What are some of the currently available options for patients with multiple myeloma?

In the upfront space, triplets are established as a standard of care. That involves a proteasome inhibitor, an immunomodulator, and a steroid. Now, we have the quadruplets where that exact same platform is integrated with a monoclonal antibody classically targeting CD38. In this case, daratumumab [Darzalex] has led that charge. Isatuximab [Sarclisa]is coming up behind, but nonetheless, I think it offers real value, particularly in the relapse setting.

Why is it impoartnt to personalize treatments for patients with multiple myeloma?

Basically, tailoring therapy to frailty to access, to minimize hospitalization, and to improve quality of life, all of these factors become important. Given that this platform is so highly active, I think it is very exciting and great that we could [tailor treatments].

Is there any ongoing research in this space that has recently caught your eye?

[I must] acknowledge the incredible advances from immunotherapy platforms and my colleagues who have led those efforts. We've seen tremendous excitement around bispecifics, we've seen tremendous excitement around chimeric antigen receptor [CAR] T, but also, [it is important] to recognize that behind that requires other approaches that are perhaps more practical, perhaps a little easier to operationalize, and these are equally valuable, in my opinion, because we have to be able to provide to our patients who are frail, elderly, perhaps on minority communities in which hospitalization is much less attractive, we may need to be able to move these new opportunities into the clinics in an absolute sense, ie become truly community based. I think that's in the future, and I think it will happen with some of the very exciting immunotherapies.

But right now, we have oral options that could also address that, as well as infusional ones that are relatively straightforward to administer, and are clearly clinically beneficial. I think amongst the oral options, we must focus on talking about the emerging excitement around CELMoDs and how useful those are. It's been my privilege to research mezigdomide [CC-92480], a particular agent that is attracting attention because it's oral and it seems to work very well, even in the face of triple-class refractory and quad refractory or BCMA-exposed disease. For patients this is an exciting way forward.

For the community oncology audience, what recommendations would provide to those treating patients with multiple myeloma?

I would offer one of continued hope, but also one of continued excitement around the novel therapies that are increasingly available. Also, understand that this complexity is understandable, and you can make sense of it. I think for some of my community oncologists, they get a little dazzled and sort of think, what do we do next? I would simply say, you can think through a paradigm now of proteasome inhibition, immunomodulation, CD38 targeting, BCMA targeting, and then how you can revisit these classes of drugs, recombine them, look at newer agents, such as the CELMoDs, such as bispecifics, and CAR T therapies, and the appropriate patient.

At the same time, also recognize that in some patients, there may be value to autologous stem cell transplant with high-dose melphalan flufenamide [Pepaxto] or newer approaches that seek to try and emulate that. I think there are a variety of takeaways that are important, and I am also excited by some of the ongoing work with immunoconjugates and antibody approaches that are simple and relatively easy to give.

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Personalizing Therapies for Optimal Outcomes in Multiple Myeloma - Targeted Oncology

Gain Therapeutics Announces Grant Award by Eurostars with Innosuisse for Alpha-1 Antitrypsin Deficiency Research Program – Marketscreener.com

Grant awarded to consortium led by Gain Therapeutics to advance the development of proprietary allosteric small molecule regulators against Alpha-1 Antitrypsin (AAT) Deficiency

BETHESDA, Md., March 21, 2023 (GLOBE NEWSWIRE) -- Gain Therapeutics, Inc. (Nasdaq: GANX), a biotechnology company transforming drug discovery with its proprietary computational discovery platform identifying novel allosteric binding sites and creating small molecule treatments, today announced that Eurostars and Innosuisse have awarded a grant in the aggregate amount of 1.2 million to a consortium led by Gain Therapeutics which includes the Institute for Research in Biomedicine, Newcells Biotech and the University of Helsinki. This grant supports a research project to develop novel small molecule allosteric regulators against Alpha-1 Antitrypsin (AAT) Deficiency, a rare genetic condition that can result in serious lung and liver diseases.

We are pleased that Eurostars and Innosuisse recognize that Gain Therapeutics allosteric small molecule regulators provide a new approach to address AAT deficiency-related metabolic diseases. We look forward to advancing our AAT program with this consortium, which combines our unique targeting approach with novel in vitro and in vivo models. This grant validates the capability of our computational discovery platform SEE-Tx to identify previously unknown allosteric binding sites on protein targets in CNS, oncology and now metabolic disease, said Dr. Manolo Bellotto, Chief Strategic Officer and General Manager at Gain Therapeutics.

Prof. Dr. Maurizio Molinari, group leader of the Protein Folding and Quality Control research team from the IRB Bellinzona and Adjunct Professor at the cole Polytechnique Fdrale de Lausanne (EPFL) added, The support by Eurostars and Innosuisse is a rewarding recognition for our long-standing activity in the field of rare diseases. The transnational collaboration with Gain Therapeutics, Newcells Biotech and the University of Helsinki will hopefully offer the opportunity to translate into the clinic, the research activity performed at the IRB and aims at understanding how perturbations in protein folding may cause severe diseases.

Dr. Mike Nicholds, CEO of Newcells Biotech added, Newcells is excited to contribute to this project and collaborate to advance an innovative therapy by applying our novel in-vitro stem cell tissue models of the liver and lung to enable efficacy and safety studies.

Dr. Satu Kuure, Principal Investigator and Head of the GM-unit at University of Helsinki commented: We are excited to participate in the Eurostars-3 project, where our task is to generate unique in-vivo models of A1AT deficiency manifesting both liver and lung symptoms. These models encompass the localized organ specific and systemic effects of A1AT deficiency. Consequently, these models will be used as a disease model where lead small molecules therapeutic power can be tested in a physiological setting.

About Alpha-1 Antitrypsin DeficiencyAlpha-1 antitrypsin deficiency is a genetic disorder that affects the production of a protein called alpha-1 antitrypsin (AAT), which is mainly produced in the liver and released into the bloodstream. AAT plays an important role in protecting the lungs from damage caused by inflammation. In people with AAT deficiency, mutations of the SERPINA1 gene cause misfolding of AAT, which then cannot be effectively released into the bloodstream. As a result, there is a buildup of the misfolded protein in the liver cells, which can cause liver damage and may lead to liver disease. Additionally, insufficient amounts of AAT in the bloodstream can lead to lung damage and the development of chronic obstructive pulmonary disease (COPD). AAT deficiency occurs in approximately 100,000 people in the United States and may qualify as an orphan disease. Gain Therapeutics has applied its drug discovery platform SEE-Tx to identify small molecules binding to a novel allosteric site on AAT to restore proper folding of the protein and halt the disease cascade leading to AAT deficiency and its associated diseases.

About Gain Therapeutics, Inc. Gain Therapeutics, Inc. is transforming drug discovery with its proprietary computational discovery platform identifying novel allosteric binding sites and creating small molecule treatments to address unmet medical needs. The ability to identify never-seen-before allosteric targets on proteins involved in diseases across the full spectrum of therapeutic areas provides opportunities for a range of drug-protein interactions, including protein stabilization, protein destabilization, targeted protein degradation, allosteric inhibition, and allosteric activation. Gains pipeline spans neurodegenerative diseases, lysosomal storage disorders (LSDs), metabolic disorders, as well as other diseases that can be targeted through protein degradation, such as oncology. Gains lead program in Parkinsons disease has been awarded funding support from The Michael J. Fox Foundation for Parkinsons Research (MJFF) and The Silverstein Foundation for Parkinsons with GBA, as well as funding support from Eurostars-3 which is part of the European Partnership on Innovative SMEs: the partnership is co-funded by the European Union through Horizon Europe and Innosuisse Swiss Innovation Agency and SERI - The State Secretariat for Education, Research and Innovation. For more information, please visit https://www.gaintherapeutics.com.

About Institute for Research in Biomedicine (IRB)The Institute for Research in Biomedicine was founded in 2000 with the clear and ambitious goal of advancing the study of human immunology, with particular emphasis on the mechanisms of host defense. The activities of the 13 research groups now extend beyond immunology to include the fields of DNA repair, rare diseases, structural and cell biology. Located in Bellinzona, capital of the Italian-speaking Canton of Ticino, the IRB is an affiliated institute of the USI Faculty of Biomedical Sciences. For more information, visit:www.irb.usi.ch

About Newcells BiotechNewcells Biotech Ltd applies its expertise and proprietary technologies in stem and primary cell biology to develop and commercialize micro-physiological systems (MPS) that closely mimic human and other species in vivo biology. Newcells unique models of the kidney and retina comprise a comprehensive suite of in-vitro MPS based assays that provide predictive insights on efficacy, safety and pharmacokinetics. The recently launched lung tissue fibrosis assay is part of a range of pulmonary models for disease modelling created by the development team that has also developed an advanced in vitro liver model.

About University of HelsinkiThe University of Helsinki is one of the worlds leading multidisciplinary research universities, renowned for its high-quality teaching, research and innovation. It is proud to be the only Finnish university constantly ranked among the top one hundred best universities in the world. The University of Helsinki has a long standing commitment for sustainability, responsibility and reflected in the motto: With the Power of Knowledge. Established in 1640, the University of Helsinki is the oldest university in Finland.

About EurostarsEurostars is a part of the Horizon Europe program that supports SMEs and project partners (universities, research organizations and other types of organizations) by funding international collaborative R&D and innovation projects. Eurostars is run by EUREKA, an intergovernmental network, which involves 37 countries.

Cautionary Note Regarding Forward-Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify these statements by forward-looking words such as "may," "might," "will," "should," "expect," "plan," "anticipate," "believe," "estimate," "predict," "goal, " "intend," "seek, " "potential" or "continue," the negative of these terms and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. All statements, other than historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, statements regarding: the development of the Companys current or future product candidates; expectations regarding timing for reporting data from ongoing preclinical studies or the initiation of future clinical trials, including the timing for completion of IND-enabling toxicology studies and submission of the dossier requirement for commencement of a Phase 1 clinical program for GT-02287 for GBA1 Parkinsons disease and the potential therapeutic and clinical benefits of the Companys product candidates; the selection and development, and timing thereof, of future programs, or any potential business development opportunities for product candidates; the Companys financial position and ability to execute on the next phase of its strategy; and the Companys anticipated cash runway guidance, including the ability for the Companys current and projected cash to allow the Company to meet value inflection points. Each of these forward-looking statements involves risks and uncertainties that could cause the Companys preclinical and future clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. These statements are not historical facts but instead represent the Company's belief regarding future results, many of which, by their nature, are inherently uncertain and outside the Company's control. Many factors may cause differences between current expectations and actual results, including the impacts of the COVID-19 pandemic and other global and macroeconomic conditions on the Companys business; clinical trials and financial position; unexpected safety or efficacy data observed during preclinical studies or clinical trials, clinical trial site activation or enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; and unexpected litigation or other disputes. Other factors that may cause the Companys actual results to differ from those expressed or implied in the forward-looking statements in this press release are identified in the sections titled Risk Factors, Managements Discussion and Analysis of Financial Condition and Results of Operations and elsewhere in the Companys Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission from time to time. New risks and uncertainties arise over time, and it is not possible for us to predict all such factors or how they may affect us. You should not place undue reliance on forward-looking statements. All information in this press release is as of the date of the release, and we are under no duty to update this information after the date of this release, except as required by law. You should not rely on it as representing our views as of any date subsequent to the date of this press release.

Investor & Media Contact:Argot PartnersNoor Pahlavi(212) 600-1902Gain@argotpartners.com

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Gain Therapeutics Announces Grant Award by Eurostars with Innosuisse for Alpha-1 Antitrypsin Deficiency Research Program - Marketscreener.com

Remarks as Prepared for Delivery by First Lady Jill Biden at the … – The White House

New Orleans, LA

Thank you, Senator Cassidy.

Its so nice to be back in New Orleans!

Dr. Ramos, Im grateful for this opportunity to see the exciting work youre doing and the progress being made. And Mayor Cantrell, Representative Boyd, Congressman Carter, thank you for the warm welcome back to this city.

Years ago, my sister Jan was diagnosed with lymphoma. Like every family that faces cancer, my sisters and I were stunned when we heard her diagnosis, terrified of losing her. But even as I held her hand, and my breath, through doctor visit after doctor visit, one thing gave me hope: that researchers like you were working tirelessly to find the best, most effective treatments for people like my sister.

For six weeks, Jan underwent stem cell transplant therapy. I visited her whenever I could. It was painful at times. But it worked. Today, thanks to her treatment and the strength she found to fight, she is a survivor.

Cancer changes everyone it touches. And in some ways, it touches us all.

This community knows that more than most. So many families here in Louisiana have lost loved ones to this disease. I know thats probably why many of you are here, why you do this work. Because you know that the breakthroughs and discoveries that you make here, every cancer-causing virus we learn how to defeat, every clinical trial that ends in success, become the miracles that our families are praying for.

Your work changes lives. And it saves them.

Thats why the Louisiana Cancer Research Center was created: because your state legislature understood that the only way we can end the devastation of this disease is by bringing researchers, and doctors, and nurses, and patients together. We see the power of that collaboration here, where LSU, Tulane, Xavier University, and Ochsner are working together under one roof and in communities throughout the state.

Today, we met nurses who are part of an incredible pilot program funded by the National Cancer Institute, revolutionizing clinical trial enrollment in remote areas throughout the southern gulf. And we saw the lab where researchers are looking for ways to stop viruses from turning healthy cells into tumors.

This work is possible because the state of Louisiana has come together. Your congressional and state representatives from both sides of the aisle, the private sector, non-profits, and academia. And one of your strongest advocates has been Senator Cassidy.

Bill, you and Dr. Cassidy have fought for patients for so long. From opening a free clinic for those most in need, to treating the uninsured, to making breast cancer screenings more accessible in this community, youve served the people of this state as doctors, and now, as public servants dedicated to investing in research to end cancer.

You understand that cancer doesnt care who someone votes for. It isnt a red or a blue issue. Its a human one. And it takes all of us, working together and sharing ideas, to stop it.

My husband, President Biden, knows that too. His Cancer Moonshot is bringing to the table the brightest minds and fiercest hearts to learn, and collaborate, and discover.

Were investing in new ways to prevent, detect, and treat cancer, and expanding access to routine screenings. That means right here, with millions of dollars from the federal government to support member institutions and scientists of the LCRC.

Today at the White House, were convening patients, survivors, companies, academic institutions, and health care providers to collaborate on efforts that will save lives from colorectal cancer.

And, in the 2024 budget that Joe released just yesterday, he is reducing the deficit and building the economy from the bottom up and the middle out, as well as investing in cancer research and prevention.

Together, across party lines and state lines were building a world where cancer is not a death sentence, where treatments are less toxic and people live longer, healthier, happier lives. Its ambitious. But its also within our reach.

For Joe and me, this is the mission of our lives. And we are ready and proud to work beside you.

Thank you.

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Remarks as Prepared for Delivery by First Lady Jill Biden at the ... - The White House

Vertex heads to the clinic with a next-gen stem cell candidate for … – Endpoints News

Vertex will start human testing of a new-and-improved version of its stem cell therapy for type 1 diabetes.

Regulators cleared Vertexs IND for its stem cell-derived pancreatic islet cell therapy VX-264 in type 1 diabetes, the company announced Thursday.

While the new candidate uses the same islet cells as VX-880, Vertexs original stem cell program for diabetes, it also makes use of an immunoprotective device that potentially eliminates the need for immunosuppression. Patients who take immunosuppressants may face a range of side effects, including an increased risk of infection. The device used in this program was invented by Semma Therapeutics, which was acquired by Vertex in 2019, and further developed at Vertex, according to a spokesperson.

The news comes several months after Vertex struck a $320 million deal to acquire ViaCyte and its other stem cell program for diabetes. The deal was intended to accelerate Vertexs overall diabetes pipeline, but did not play into the development of either VX-880 or VX-264, according to the company.

Both companies had been attempting to rejuvenate patients abilities to produce their own insulin using stem cell transplants. ViaCyte was going for an off-the-shelf gene-edited approach encapsulated in immune-evading devices that researchers thought could prevent rejection.

VX-880 has successfully demonstrated clinical proof of concept in T1D, and the acquisition of ViaCyte will accelerate our goal of transforming, if not curing T1D by expanding our capabilities and bringing additional tools, CEO Reshma Kewalramani said in a statement at the time.

Vertex plans to launch a Phase I/II trial in the first half of this year and is already conducting a Phase I/II in Canada, it said on Thursday.

Editors Note: This story has been updated throughout to reflect that ViaCytes technology was not used in the development of VX-880 or VX-264. A previous version of this story incorrectly stated that VX-264 was developed using technology from the ViaCyte acquisition. The story has been corrected to reflect that the device used in this program was invented by Semma Therapeutics, which was acquired by Vertex in 2019, and further developed at Vertex.

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Vertex heads to the clinic with a next-gen stem cell candidate for ... - Endpoints News

4 Big Things You Should Know About Primary Immunodeficiency Diseases – Self

As humans, weve been living alongside viruses, bacteria, fungi, and other pathogens for as long as weve existedand weve developed pretty hardy immune systems to deal with them. Unfortunately, in rare cases, some people are born with genetic errors in their immune systems that might make even the mildest bug a serious foe. Many of the symptoms of these conditions first start to appear in childhoodeven in infantsbut others dont present themselves until well into adulthood.

Primary immunodeficiency diseases (PIDDs)now commonly referred to as inborn errors of immunity (IEIs)1is a group of genetic diseases that cause the immune system to malfunction,Dusan Bogunovic, PhD, a professor at the Precision Immunology, Mindich Child Health and Development, and Icahn Genomics institutes in New York City, tells SELF.

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For some people, the immune system malfunctions by not mounting enough of a defense against harmful pathogens, which can result in stubborn infections that lead to frequent illnesses. For others, genetic errors can actually cause the immune system tooverfunction, or put up a fight when its not necessary, which can harm the bodys healthy tissues in the process. Some PIDD conditions, such asWiskott-Aldrich syndrome, are characterized by an underperformingand an overperforming immune system, according toXiao Peng, MD, PhD, an assistant professor of genetic medicine and the director of the Genetics of Blood and Immunity Clinic at Johns Hopkins University School of Medicine. So not only is the immune system insufficiently capable of attacking the things that it should be, sometimes it likes to go rogue and attack the things that it shouldnt be, she tells SELF.

All of this is to say that the immune system is undeniably complex, and experts are still learning about all of the genes involved in PIDDs. Heres what you should know about this umbrella of diseasesincluding the kinds of symptoms that might be worth exploring further.

Most PIDDs are caused by an erroror several errorsin a persons genes, Dr. Peng says. For example, they may have inherited damage to a variant in a single gene.1 In turn, they may experience frequent infections or chronic inflammation, and this can set the stage for serious health problems, Dr. Bogunovic saysall because the immune system isnt quite working right.

These diseases also run on a spectrum, Dr. Peng says. On the most severe end, there are cases likeDavid Vetter, a young boy from Texas who had severe combined immunodeficiency (SCID); he made national news because he had to live in a plastic bubble to protect himself from a number of infectious pathogens until he died at age 12. (Newborns are routinely screened for SCID, among a few other PIDDs.2) Other PIDDs, however, may only make a person more likely to experience complications to a very specific type of pathogen that they dont get exposed to until much later in life, if at all.

It really depends on the person. Even if two people are diagnosed with the same PIDD, one person may end up getting very sick, while another lives a generally healthy life. Some people might have antibody deficiencies that you can measure on a lab test, but [they] never get super sick, Dr. Peng says. That speaks to the fact that what your cells are doing is not necessarily what your body and your environment are putting you at risk for.

That said, one potential indicator that you have an inborn error of immunityis that youre getting severely sick on a regular basiswhich well talk more about in a second.

There are nearly 500 different PIDDs that experts are aware of, and that number is growingmore than 100 new gene errors that contribute to these diseases are discovered every year, according to Dr. Peng.3

When you look at each PIDD individually, each type is relatively rare; collectively, however, these conditions are estimated to affect up to 5 in every 1,000 peopleand certain PIDDs are more frequently diagnosed than others.3 The most common PIDDs affect the bodys ability to produce antibodies, protective proteins that attach to harmful pathogens and remove them from your body. For example, common variable immunodeficiency (CVID), one of the most common PIDDs diagnosed, causes people to have low levels of blood immunoglobulins (another name for antibodies), which can increase their risk of infection, according to theImmune Deficiency Foundation (IDF). Its estimated to affect about 1 in 25,000 people.

Another common PIDD is selective IgA deficiencyas many as 1 in 500 white people have it, but research is lacking to determine the prevalence in people of color. IgA deficiency means an important type of immunoglobulin, immunoglobulin A (IgA), is undetectable in the blood, even though other types of immunoglobulin in the body are detected at normal levels.4 People with IgA deficiency often complain of frequent ear infections, sinusitis, bronchitis, and pneumonia that might not resolve with regular treatment, the IDF notes. They may also have issues with their gut health (including gastrointestinal infections or chronic diarrhea), or have autoimmune conditions, Dr. Peng says, like celiac disease, lupus, or rheumatoid arthritis.

Remember: Not everyone who is diagnosed with PIDDs gets sick a lotplenty of people who have the selective IgA deficiency dont end up seeing the doctor any more often than other folks, while others end up severely ill. Doctors arent sure why that is yet.

When it comes to PIDDs, the biggest red flags include:

Other possible symptoms of PIDDs include digestive issues, delayed growth or development, or inflammation of the internal organs, according to the Mayo Clinic.

Unfortunately, identifying a PIDD can take a while. On average, it takes people more than six years to get an accurate diagnosis, which can be fatal in some cases, Dr. Bogunovic says.5 There are lots of reasons a diagnosis can be delayed, he says, including that primary immunodeficiency diseases sometimes dont appear until later in a persons life, primary care doctors arent always aware of the vast range of PIDDs or their unique symptoms, and it might be difficult for some people to access the right experts (like an immunologist) or credible institutions for both geographic and socioeconomic reasons.

The good news is, thats not always the case. Dr. Peng has been on care teams that provided patients with a diagnosis within a week, thanks to experts working together on several fronts and diving into the persons genetics and medical history.

When it comes to PIDD treatments, there are a few options, and each has potential pros and cons. They fall into the following three broad categories.

This is often the most accessible avenue, and lots of people diagnosed with PIDDs do well by managing infections for years and years, Dr. Peng says. For example, according to theMayo Clinic, if you have frequent bacterial infections, longer courses of antibiotics or intravenous antibiotics may be recommended. Long-term antibiotic use may help to ward off an infection before it starts too. If a person is lacking certain antibodies, immunoglobulin therapytypically an IV treatmentcan help replace the lacking proteins.

This can be done via a bone marrow or stem cell transplant.6 For astem cell transplant, a doctor takes stem cells (a.k.a. blood-forming cells) from a donor with a healthy immune system. The doctor also wipes out the patients immune system (essentially erasing the genetic errors in question). Then, healthy stem cells from a donor are put into the blood of the patient. These new stem cells replicate over time, completely replacing the persons formerly malfunctioning immune system. Unlike with managing symptoms, if all goes well, the patient is cured.

Unfortunately, Dr. Peng says, moving forward with a stem cell transplant is not a simple decision for the doctor or the patient. Youre basically knocking out all of the persons immune defenses, putting them at incredible risk for infection before you give them back someone elses stem cells, she says. Even after the cells have been transferred to the person receiving the transplant, it takes time for whats essentially a brand-new immune system to reach fighting capacity. Unfortunately, theres also a risk that the donors new cells will view the recipients body as a threat and start attacking otherwise healthy tissues, Dr. Peng says. Genetic testing is critically important when screening candidates for a stem cell transplant, she adds, because some genetic errors live elsewhere in the body, not just the stem cells.

Unlike a stem cell transplant, in gene therapy, technology is used to extract a patients own stem cells, edit the PIDD-related genetic error out of a persons stem cells, then deliver the corrected stem cells back into their body intravenously, per the Mayo Clinic. Most gene therapy is in its early stages and not ready for patient use yet, Dr. Peng says, but there are severalclinicaltrials that are currently testing these therapies on humans. According to theImmune Deficiency Foundation, there are only a few current use cases for gene therapy outside of these trials, including for children with certain types of SCID.

Finally, many people reduce their risk of infection with the basic protective protocols youre probably already familiar with: practicing good hygiene like handwashing, eating well, exercising regularly, and avoiding people who are actively sick, the Mayo Clinic notes.

I think a lot of it is just providing families with information about the nature of that particular immune disease and what their risks are and what situations they need to be a little bit more vigilant [about], Dr. Peng says. Its crucial to find balance too, to make sure their lives dont become entirely about avoidance. Some of the most common sense, simple things are also the most useful things.

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4 Big Things You Should Know About Primary Immunodeficiency Diseases - Self

Caribou Biosciences Reports Fourth Quarter and Full Year 2022 … – Yahoo Finance

Caribou Biosciences, Inc.

-- CB-010 ANTLER Phase 1 trial in r/r B-NHL ongoing with update planned for H2 2023 --

-- CB-011 CaMMouflage Phase 1 trial in r/r MM recruiting patients at dose level 1 --

-- CB-012 IND-enabling studies initiated; IND submission in r/r AML planned for H2 2023 --

-- $317.0 million in cash, cash equivalents, and marketable securities as of December 31, 2022; cash runway to fund the current operating plan into 2025 --

BERKELEY, Calif., March 09, 2023 (GLOBE NEWSWIRE) -- Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, today reported financial results for the fourth quarter and full year 2022 and reviewed recent pipeline progress.

We successfully demonstrated the potential of our chRDNA genome-editing technology with promising clinical data from CB-010, our lead allogeneic cell therapy, said Rachel Haurwitz, PhD, Caribous president and chief executive officer. The initial dose level of CB-010 demonstrated 6-month complete response rates that have the potential to rival the responses seen with approved autologous CAR-T cell therapies. We are excited that the FDA granted the CB-010 program RMAT and Fast Track designations last year. Our team drove additional pipeline progress with an IND clearance for CB-011, enabling us to activate clinical sites for our CaMMouflage Phase 1 trial. In 2023, Caribou plans to maintain this momentum by advancing two ongoing clinical trials for our off-the-shelf cell therapies in patients with hematologic malignancies and preparing an IND submission for our third program, CB-012.

Accomplishments and Highlights

Pipeline and Technology

CB-010: Caribou reported promising data at dose level 1 (40x106 CAR-T cells) from its ongoing ANTLER Phase 1 clinical trial of CB-010 in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL).

Following a single infusion of CB-010 at dose level 1, all 6 patients in cohort 1 achieved complete responses as their best response. 3 of 6 patients maintained complete responses at 6 months, with 2 of 6 maintaining complete responses at 12 months. Caribou plans to provide an update from the ongoing ANTLER Phase 1 trial for CB-010 in H2 2023.

Clinical data presentations are available on Caribous website under Scientific Publications.

Following demonstration of an encouraging safety profile at dose level 2 (80x106 CAR-T cells), with no dose-limiting toxicities (DLTs) in the 3 patients treated, Caribou continues to enroll patients at dose level 3 (120x106 CAR-T cells).

The U.S. Food and Drug Administration (FDA) has granted CB-010 Regenerative Medicine Advanced Therapy (RMAT), Fast Track, and Orphan Drug designations. These designations provide important benefits in the drug development process and are designed to facilitate and expedite development and regulatory review, including providing eligibility for priority and rolling reviews and accelerated approval, if relevant criteria are satisfied.

CB-010 is the first allogeneic anti-CD19 CAR-T cell therapy in the clinic, to Caribous knowledge, with a PD-1 knockout (KO), a genome-editing strategy designed to improve antitumor activity by limiting premature CAR-T cell exhaustion.

Additional information on the ANTLER trial (NCT04637763) can be found at clinicaltrials.gov.

CB-011: Caribou recently activated clinical sites for the recruitment of patients at dose level 1 (50x106 CAR-T cells) of CB-011 in the CaMMouflage Phase 1 trial for relapsed or refractory multiple myeloma (r/r MM).

CB-011 is the first allogeneic CAR-T cell therapy in the clinic, to Caribous knowledge, that is engineered to improve antitumor activity through an immune cloaking strategy with a B2M KO and insertion of a B2MHLA-E fusion protein to blunt immune-mediated rejection.

Preclinical data for CB-011 were presented in a poster at the 2023 Tandem Meeting: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, February 15-19, 2023, in Orlando, Florida. The poster presentation is available on Caribous website under Scientific Publications.

Additional information on the CaMMouflage trial (NCT05722418) can be found at clinicaltrials.gov.

CB-012: Caribou has initiated IND-enabling studies for CB-012, an allogeneic anti-CLL-1 CAR-T cell therapy, to support a planned IND application submission for relapsed or refractory acute myeloid leukemia (r/r AML).

CB-012 is the first allogeneic CAR-T cell therapy, to Caribous knowledge, with both checkpoint disruption, through a PD-1 KO, and immune cloaking, through a B2M KO and B2MHLA-E fusion protein insertion; both armoring strategies are designed to improve antitumor activity. CB-012 is engineered with 5 genome edits, enabled by Caribous next-generation CRISPR technology platform, which uses Cas12a chRDNA genome editing to significantly improve the specificity of genome edits.

In preclinical AML models, CB-012 significantly reduced tumor burden and increased overall survival compared to controls.

CB-020: Caribous first induced pluripotent stem cell (iPSC)-derived allogeneic CAR-NK cell therapy, CB-020, is designed to target solid tumors expressing the tumor antigen ROR1.

Preclinical data supporting the selection of the ROR1 CAR construct and armoring strategies for the companys CAR-NK cell platform were presented at the 12th American Association for Cancer Research and Japanese Cancer Association (AACR-JCA) Joint Conference in December 2022. The poster presentation is available on Caribous website under Scientific Publications.

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Anticipated 2023 Milestones

CB-010: Caribou plans to provide an update from the ongoing ANTLER Phase 1 trial for CB-010 in H2 2023.

CB-011: Caribou recently activated clinical sites for the recruitment of patients at dose level 1 and plans to provide an update on the clearance of dose levels as appropriate from the CaMMouflage Phase 1 trial for CB-011.

CB-012: Caribou plans to submit an IND application for CB-012 in H2 2023.

Upcoming Investor Conferences

Fourth Quarter and Full Year 2022 Financial Results

Cash, cash equivalents, and marketable securities:Caribou had $317.0 million in cash, cash equivalents, and marketable securities as of December 31, 2022, compared to $413.5 million as of December 31, 2021. Caribou expects these cash, cash equivalents, and marketable securities will be sufficient to fund its current operating plan into 2025.

Licensing and collaboration revenue: Revenue from Caribous licensing and collaboration agreements was $3.7 million for the three months ended December 31, 2022 and $13.9 million for the full year 2022, compared to $2.6 and $9.6 million, respectively, for the same periods in 2021. The increases were primarily due to revenue recognized under the AbbVie Agreement.

R&D expenses:Research and development expenses were $25.7 million for the three months ended December 31, 2022 and $82.2 million for the full year 2022, compared to $15.1 and $52.3 million, respectively, for the same periods in 2021. The increases were primarily due to costs to advance pipeline programs; increased headcount, including stock-based compensation; facilities and other allocated expenses; and increased external manufacturing and clinical activities.

G&A expenses:General and administrative expenses were $8.5 million for the three months ended December 31, 2022 and $38.0 million for the full year 2022, compared to $7.9 and $24.3 million, respectively, for the same periods in 2021. The increases were primarily due to increased headcount, including stock-based compensation; legal, accounting, insurance, and other expenses necessary to support the growth and operation of a clinical-stage public company; and facilities and other allocated expenses.

Net loss: Caribou reported a net loss of $27.0 million for the three months ended December 31, 2022 and $99.4 million for the full year 2022, compared to $18.5 and $66.9 million, respectively, for the same periods in 2021.

About Caribous Novel Next-Generation CRISPR Platform CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells. There are two basic components of Class 2 CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems are capable of editing unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and phenotype. In response to this challenge, Caribou has developed CRISPR hybrid RNA-DNA guides (chRDNAs; pronounced chardonnays) that direct substantially more precise genome editing compared to all-RNA guides. Caribou is deploying the power of its Cas12a chRDNA technology to carry out high efficiency multiple edits, including multiplex gene insertions, to develop CRISPR-edited therapies.

About Caribou Biosciences, Inc.Caribou Biosciences is a clinical-stage CRISPR genome-editing biopharmaceutical company dedicated to developing transformative therapies for patients with devastating diseases. The companys genome-editing platform, including its proprietary Cas12a chRDNA technology, enables superior precision to develop cell therapies that are armored to potentially improve antitumor activity. Caribou is advancing a pipeline of off-the-shelf cell therapies from its CAR-T and CAR-NK platforms as readily available treatments for patients with hematologic malignancies and solid tumors.

Follow us @CaribouBio and visit http://www.cariboubio.com.

Caribou Biosciences and the Caribou logo are registered trademarks of Caribou Biosciences, Inc.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements related to Caribous strategy, plans, and objectives, and expectations regarding its clinical and preclinical development programs, including its expectations relating to the timing of updates from its ANTLER Phase 1 clinical trial for CB-010 as well as the status and updates from its CaMMouflage Phase 1 clinical trial for CB-011, expectations about product developments in 2023, and the submission of an IND application for CB-012. Management believes that these forward-looking statements are reasonable as and when made. However, such forward-looking statements are subject to risks and uncertainties, and actual results may differ materially from any future results expressed or implied by the forward-looking statements. Risks and uncertainties include, without limitation, risks inherent in the development of cell therapy products; uncertainties related to the initiation, cost, timing, progress, and results of Caribous current and future research and development programs, preclinical studies, and clinical trials; and the risk that initial or interim clinical trial data will not ultimately be predictive of the safety and efficacy of Caribous product candidates or that clinical outcomes may differ as more patient data becomes available; the risk that preclinical study results we observed will not be borne out in human patients; as well as other risk factors described from time to time in Caribous filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2022 and subsequent filings. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. Except as required by law, Caribou undertakes no obligation to update publicly any forward-looking statements for any reason.

Caribou Biosciences, Inc.Condensed Consolidated Balance Sheet Data(in thousands) (unaudited)

December 31,2022

December 31,2021

Cash, cash equivalents, and marketable securities

$

317,036

$

413,508

Total assets

373,765

442,356

Total liabilities

72,894

54,531

Total stockholders' equity

300,871

387,825

Total liabilities and stockholders' equity

$

373,765

$

442,356

Caribou Biosciences, Inc.Condensed Consolidated Statement of Operations(in thousands, except share and per share data)(unaudited)

Three Months EndedDecember 31,

Year EndedDecember 31,

2022

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Caribou Biosciences Reports Fourth Quarter and Full Year 2022 ... - Yahoo Finance

What Causes a Weakened Immune System? – Self

Youve probably heard a lot about how important your immune system is, especially over the past few years. Phrases like herd immunity and immunocompromised proliferated in official public health updates, news stories, and health care centers as experts navigated all the uncertainties of the COVID-19 pandemic. Now, we know that the virus can affect anyone, but it can lead to particularly risky complications for the most vulnerable people in our communities.1

Of course, theimmune systems job is to protect your body fromall invaders that may be harmful, not just certain viruses: When functioning properly, it alerts your body to a wide range of potential threats and helps it respond accordingly. However, some people have dysfunctional immune systemswhich are also known as weakened or compromised immune systemsthat cause their bodies protective response to be under- or overactive, perJohns Hopkins Medicine.

Theres no exact figure for how many people live with weakened immune systems, but its safe to say its in the millions,Leonard Calabrese, DO, a rheumatologic and immunologic disease expert at the Cleveland Clinic, tells SELF. Some research suggests at least 7 million adults in the United States are immunocompromised, per theCenters for Disease Control and Prevention (CDC).

Below, experts explain the factors that can break down the immune systems defenses, the common symptoms associated with compromised immune systems, and what kinds of treatments are available to help.

What is a weakened immune system, exactly?

Yourimmune system is an intricate network of cells, tissues, and organs (as well as the substances they make) that, generally speaking, fight disease and infection, according to the National Institutes of Health (NIH). White blood cells may come to mind, but there are lots of body parts that play important roles in your immune health, like your skin, lymph nodes and vessels, thymus gland (which makes white blood vessels), spleen, tonsils, and bone marrow, among others.

The immune system is generally broken down into two parts,Scott Weisenberg, MD, an infectious disease specialist at NYU Langone Health, tells SELF. These are called the innate (or inherited) and the adaptive (or acquired) immune systems. The major difference between the two is that youre born with the former and your body develops the latter.2 Theinnate immune system is the first to respond to an invadersuch as a harmful germby surrounding it with protective cells and, if all goes as planned, killing it. Theadaptive immune system supports your innate response by producing proteins called antibodies.2 These are designed to counter a specific threat, like certain viruses or bacteria, should your body be exposed to them and need backup in the future, perJohns Hopkins Medicine.

Problems can occur when the immune system either doesnt respond enough or responds too strongly, Dr. Calabrese says. A compromised immune system fails to either detect danger or [reacts] aggressively and causes collateral damage to our systems, he explains.3 Its worth noting that problems with the immune system exist on a spectrum, Dr. Calabrese adds. The potential health risks posed by a weakened immune system arent the same if youre comparing one person who, for example, has moderate allergies, to someone whod recently had an organ transplant. Theyre hardly in the same category, Dr. Calabrese says.

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What causes a weakened immune system?

Any number of health issues, such as mild asthma, can affect your bodys ability to fight disease and infectionand certain lifestyle factors, like smoking tobacco and not getting enough sleep, can also interfere with your bodys ability to stay balanced and heal, theCDC says. However, there are several major factors that can compromise your immune systems defenses. These include:

Autoimmune diseases are characterized by a malfunctioning immune response; essentially, your body goes a bit rogue and starts to attack its healthy cells, tissues, and organs, according to theNIH. There are more than 80 autoimmune diseases that experts know of, includingrheumatoid arthritis,type 1 diabetes,lupus, and many more; these conditions are thought to impact at least 24 million people in the United States, while an additional 8 million are estimated to have blood markers that point to their susceptibility of developing one of these disorders, per the NIH.

Autoimmune diseases in general compromise a persons immune system by attacking the body. On top of that, to help a person manage the symptoms caused by their conditionmany of which can severely affect the persons quality of lifeexperts often recommend medications called immunosuppressants, like steroids orbiologics. These medications can be life-changing for some people but, in turn, the treatments can weaken the entire immune system or just a specific part of it, according to theAmerican Academy of Allergy Asthma & Immunology.

People who receive a bone marrow, stem cell,4 or organ transplant will also have a weakened immune system during the first few weeks after the procedure because the bodys white blood cell count is depleted, increasing the risk of potential infection. Immunosuppressants are also commonly prescribed following these procedures because they help the body accept the transplant and prevent it from attacking normal (and vital) tissues, according to experts at theUniversity of Pennsylvania Health System.

Primary immunodeficiency diseases (PIDDs)also commonly known as inborn errors of immunityare rare genetic disorders that cause at least one part of a persons immune system to malfunction, according to theNIH. There are nearly 500 known PIDDs, and theyre typically characterized by repeated or severe infections.5

There are a variety of other health conditions including type 2 diabetes, liver or kidney diseases, alcohol use disorder, and HIV/AIDS, among others,that can compromise your immune system, theCDCnotes. Any form of cancer can also weaken or suppress the immune system, per theAmerican Cancer Society, but the associated treatments, which tend to be really hard on the body, can mess with immune defenses as well. These can include chemotherapy, radiation, surgery, stem cell transplants, and more.

These conditions are known as secondary immunodeficiencies, which are far more common than primary immunodeficiencies. Secondary immunodeficiencies are not a result of geneticerrors, but rather a variety of potential factors that can impact a persons once-normal immune system, like an infectious pathogen, certain substances, and environmental changes, for example.6

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What are some common signs of having a weakened immune system?

Immunocompromised people tend to get infections more often, or they may get severely ill from infections that people with healthy immune systems can recover from more easily, Dr. Weisenberg says. This means the infections may be harder to treat or last longer than expected.

People with weakened immune systems are also more likely to experience symptoms triggered by germsincluding viruses, bacteria, and fungithat arent normally seen in people with healthy immune systems. For example, Dr. Weisenberg says, a serious infection causedby the fungus Pneumocystis jiroveciiis usually only detected in people with weakened immune systems.

Frequentdigestive issues, like diarrhea, constipation, and gas, are also worth noting, per theUniversity of Pennsylvania Health System. (One theory that might explain this: Research suggests a large portion of the immune system lives in the gastrointestinal tract. In fact, up to 80% of your immune cells are found in the gut.7)

Minor woundssuch as cuts and scrapesmay also be slower to heal, since healthy immune cells are needed to shepherd the recovery process.

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What kinds of treatments are available for people with weakened immune systems?

The best treatment plan will vary depending on what, exactly, is compromising a persons immune system, Dr. Weisenberg says. In general, many treatment plans are focused on symptom management and infection control. Some people may also benefit fromintravenous immunoglobulin therapy to help replenish protective proteins, namely antibodies, and prevent infection, he adds. Immune system replacement in the form of stem cell or bone marrow transplants, as well as gene therapy, are also options depending on the cause and severity of a persons condition,as SELF previously reported.

Even with these care options, its important to recognize that people with weakened immune systems often depend on herd immunity or community immunity. This is achieved when a majority of a population has a sufficient level of immunity against aspecific infectious disease through vaccination or prior infection and recovery. This helps reduce the person-to-person spread of a pathogen, ultimately protecting vulnerable people who cant afford to get sick due to a higher risk of complications or who dont respond to or cant receive certain vaccines.8

Community immunity is extremely important,Dusan Bogunovic, PhD, a professor of microbiology at the Icahn School of Medicine at Mount Sinai in New York City, tells SELF. This can be a lifeline for many.

There are other common-sense strategies that slow infection in our communities, too, like frequent handwashing and masking up in crowded spaces. It takes a collective, conscious effort: Together, we can help protect the millions of immunocompromised people we live, work, and hang out with every day.

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What Causes a Weakened Immune System? - Self

Olema Oncology to cut 25% of staff, says it will focus on late-stage … – Endpoints News

Olema Oncology will let go of a quarter of its workforce, as well as two top executives, as the biotech works to keep alive work on an experimental breast cancer drug that has so far been a disappointment.

The cuts will affect workers in R&D and corporate functions, the company said in a press release Thursday. Also out are CBO Kinney Horn and Cyrus Harmon, a co-founder of the company and its chief research officer. Harmon will stay as a member of the board. The company had 83 full-time employees as of Jan. 31, according to a financial filing.

CEO Sean Bohen has led the company since he left the top medical spot at AstraZeneca. The job cuts will let the company focus resources on OP-1250, the breast cancer drug that has worked and struggled with to move forward for years.

Given the challenging equity market environment, we made some difficult decisions regarding our organization and earlier-stage programs, Bohen said in the press release.

The company is worth a fraction of its value from when it IPOed in 2020, and the shares were trading around $50 a share. In November 2021, it announced results from its Phase I/II trial of OP-1250 that greatly disappointed investors because of the low response rate in advanced ER+/HER2- breast cancer. The stock plunged and has never recovered, and now trades around $4 a share.

The San Francisco-based biotech says it has enough cash to last into 2025. It reported $204.4 million in cash, equivalents and marketable securities as of the end of last year and a net loss of $104.8 million.

It plans to start a Phase III trial of OP-1250, an estrogen receptor antagonist, in the second half of the year, as a second- and third-line treatment for metastatic breast cancer. And it has Phase II trials that it expects will report out this year, both as a monotherapy and in combination with Pfizers Ibrance.

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Olema Oncology to cut 25% of staff, says it will focus on late-stage ... - Endpoints News

Dr. Shah on the Safety of LV20.19 CAR T-cell Therapy in R/R MCL – OncLive

Nirav N. Shah, MD, associate professor, Medical College of Wisconsin, discusses the safety of the lentiviral bispecific CAR T cells targeting CD20 and CD19 B-cell antigens (LV20.19 CAR), as well as future efforts from a phase 1/2 study (NCT04186520) of the product in patients with relapsed/refractory mantle cell lymphoma (MCL).

At the 2023 Transplantation and Cellular Therapy Meetings, investigators presented data on the single-center, prospective study that examined 14 patients. The trial met its primary end point with an overall response rate (ORR) of 100% at day 28, including a 71% complete response (CR) rate. At day 90, the ORR remained at 100%, and the CR rate improved to 92%.

Regarding safety, findings for the use of LV20.19 CAR in patients with MCL have been in line with other histologies treated with the agent, Shah says. Thirteen of 14 patients (93%) experienced grade 1/2 cytokine release syndrome (CRS); however, there were no instances of grade 3/4 CRS. Two patients (14%) had grade 3/4 immune-effector cell-associated neurotoxicity syndrome (ICANS), and 1 patient (7%) had grade 1/2 ICANS.

Shah notes that no patients required intensive care unitlevel care in the first 28 days; however, 1 non-relapse mortality was reported in a high-risk patient who previously received an allogeneic stem cell transplant for MCL, then subsequently relapsed and received CAR T-cell therapy, Shah explains. This patient died from gram-negative sepsis at day 46, Shah adds. Beyond the lone non-relapse mortality, LV20.19 CAR was well tolerated, and all patients remained alive at data cutoff, Shah continues.

The safety and efficacy profiles of this agent are favorable compared with currently available agents, Shah notes. Investigators next hope to evaluate LV20.19 CAR in patients with relapsed/refractory MCL in a multicenter setting, Shah concludes.

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Dr. Shah on the Safety of LV20.19 CAR T-cell Therapy in R/R MCL - OncLive

Investigating KRAS/TP53 Co-Alterations in Pancreatic Cancer – Targeted Oncology

Jashodeep Datta, MD, a surgical oncologist at Sylvester Comprehensive Cancer Center and assistant professor of Clinical at the University of Miami Miller School of Medicine, explains KRAS co-alteration in patients with pancreatic cancer.

Many pancreatic tumors have co-alterations in KRAS and TP53, explains Datta. The reason for these co-alterations is unknown, and oncologists also do not have a clear picture of how this effects the disease. These questions were explored preclinically and warrant further study.

0:07 | We are very interested in understanding the chasm that exists between the genotype of pancreas cancer and the virulent phenotype of pancreas cancer. What makes it so hostile for patients? To do that we approach this from the genome of the pancreatic cancer cell, which is really the incipient event in pancreatic tumorigenesis. And what's very interesting about pancreas cancer is compared with all of the cancers, if you look across the Cancer Genome Atlas, pancreatic cancer is the number one cancer that has cooperated mutations of KRAS and TP53.

0:46 | We really want to understand if there is a biologic basis for that, and what are the downstream repercussions of that. The was really the basis of this study. The most important finding that really paved the way for the remainder of our study was our finding, using a cohort of 250 patients from the University of Miami, as well as validation in two independent datasets, one from the Cancer Genome Atlas, as well as one from an international molecularly annotated data set the ICGC, where we showed that patients who had quadrate mutations in KRAS and TP53 had worse survival and worse prognosis compared with patients who had mutations in either the carrier s gene alone. And they had may have other mutations, but not TP53, or TP53 mutations alone, but not KRAS. So, this really paved the foundation for the remainder of the study.

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Investigating KRAS/TP53 Co-Alterations in Pancreatic Cancer - Targeted Oncology