BioRestorative Therapies to Present at the Emerging Growth Conference on June 9, 2021 – StreetInsider.com

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BioRestorative Therapies invites individual and institutional investors, as well as advisors and analysts, to attend its real-time, interactive presentation at the online Emerging Growth Conference.

MELVILLE, N.Y., June 07, 2021 (GLOBE NEWSWIRE) -- BioRestorative Therapies, Inc. (the Company or BioRestorative) (OTC: BRTX), a life sciences company focused on stem cell-based therapies, is pleased to announce that it is has been invited to present at the online Emerging Growth Conference on June 9, 2021.

The Emerging Growth Conference will be held on June 9, 2021. This live, interactive online event will give existing shareholders and the investment community the opportunity to interact with the Companys CEO, Lance Alstodt, and Vice President of Research and Development, Francisco Silva, in real time.

Mr. Alstodt will make a presentation and answer questions. Please ask your questions during the event and Mr. Alstodt will try to respond to as many as possible.

BioRestorative Therapies will be presenting at 10:45 AM Eastern time for 45 minutes.

Please register here to ensure you are able to attend the conference and receive any updates that are released:

https://goto.webcasts.com/starthere.jsp?ei=1469230&tp_key=f8b5116237&sti=brtx

If attendees are unable to join the event live on the day of the conference, an archived webcast will also be made available on EmergingGrowth.com, and the Company will also release a link to that site after the event.

About the Emerging Growth Conference

The Emerging Growth Conference is an effective way for public companies to present and communicate their new products, services and other major announcements to the investment community from the convenience of their office, in a time efficient manner.

The Conferences focus and coverage includes companies in a wide range of growth sectors, with strong management teams, innovative products and services, focused strategy, execution, and the overall potential for long term growth. Its audience includes potentially tens of thousands of individuals and institutional investors, as well as investment advisors and analysts.

All sessions will be conducted through video webcasts and will take place in the Eastern time zone.

About BioRestorative Therapies, Inc.

BioRestorative Therapies, Inc. (www.biorestorative.com) develops therapeutic products using cell and tissue protocols, primarily involving adult stem cells. Our two core programs, as described below, relate to the treatment of disc/spine disease and metabolic disorders:

Disc/Spine Program (brtxDISC): Our lead cell therapy candidate, BRTX-100, is a product formulated from autologous (or a persons own) cultured mesenchymal stem cells collected from the patients bone marrow. We intend that the product will be used for the non-surgical treatment of painful lumbosacral disc disorders or as a complementary therapeutic to a surgical procedure. The BRTX-100 production process utilizes proprietary technology and involves collecting a patients bone marrow, isolating and culturing stem cells from the bone marrow and cryopreserving the cells. In an outpatient procedure, BRTX-100 is to be injected by a physician into the patients damaged disc. The treatment is intended for patients whose pain has not been alleviated by non-invasive procedures and who potentially face the prospect of surgery. We have received authorization from the Food and Drug Administration to commence a Phase 2 clinical trial using BRTX-100 to treat chronic lower back pain arising from degenerative disc disease.

Metabolic Program (ThermoStem): We are developing a cell-based therapy candidate to target obesity and metabolic disorders using brown adipose (fat) derived stem cells to generate brown adipose tissue (BAT). BAT is intended to mimic naturally occurring brown adipose depots that regulate metabolic homeostasis in humans. Initial preclinical research indicates that increased amounts of brown fat in animals may be responsible for additional caloric burning as well as reduced glucose and lipid levels. Researchers have found that people with higher levels of brown fat may have a reduced risk for obesity and diabetes.

Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events or results to differ materially from those projected in the forward-looking statements as a result of various factors and other risks, including, without limitation, those set forth in the Company's latest Form 10-K filed with the Securities and Exchange Commission. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. Any forward-looking statements in this release are made as of the date hereof and the Company undertakes no obligation to update such statements.

CONTACT: Email: ir@biorestorative.com

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BioRestorative Therapies to Present at the Emerging Growth Conference on June 9, 2021 - StreetInsider.com

Novel CAR-T Cell Therapy Produces Early and Deep Responses in Certain Patients with Multiple Myeloma – Curetoday.com

Treatment with a single infusion of the novel CAR-T cell therapy ciltacabtagene autoleucel (cilta-cel) induced early and deep responses in a group of patients with relapsed/refractory multiple myeloma, according to results of a phase 2 study.

The findings, which were presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated that a single-infusion of the CAR-T cell therapy resulted in an overall response rate (which includes a partial response or better) of 95% with a stringent complete response rate of 75%, and a very good partial response rate or better of 85%.

Cilta-cel, formerly JNJ-68284528, is a second-generation CAR-T cell therapy with two BCMA-targeting, single-domain antibodies designed to confer avidity. Previous data that were published from the phase 1b/2 CARTITUDE-1 trial demonstrated that single infusion of cilta-cel was associated with deep and durable response among heavily pretreated patients with relapsed/refractory disease.

Measuring minimal residual disease negativity, or the small number of cancer cells in the body after cancer treatment, was the main goal of the study. Other goals included assessing overall response rate, duration of response, as well as time and duration of minimal residual disease negativity and incidence and severity of side effects.

The study comprised 20 patients (median age, 60 years; 65% men) who were either refractory to treatment with the chemotherapy lenalidomide or relapsed after one to three prior lines of treatment. One of the patients was treated in an outpatient setting.

Twelve of the patients had received fewer than three lines of prior therapy, and the remaining individuals received three prior lines of therapy.

All the patients had been previously treated with a proteasome inhibitor, an immunomodulatory drug and the steroid dexamethasone. Almost all (95%) of the patients were exposed to alkylating agents, and 65% received treatment with Darzalex (daratumumab).

As of the data cutoff of January 2021, four evaluable patients achieved minimal residual disease negativity.

Blood-related side effects that occurred in 20% or more of the patients included neutropenia (95%), thrombocytopenia (80%), anemia (65%), lymphopenia (60%) and leukopenia (55%). Moreover, cytokine release syndrome (which involves the cytokines overstimulating the immune system so that it attacks healthy organs) occurred in 85% of patients, of which 10% were considered serious or severe.

The safety profile was manageable, including in the one patient that was treated in the outpatient setting, said study author Dr. Mounzer E. Agha, director of the Mario Lemieux Center for Blood Cancers and clinical director of Hematopoietic Stem Cell Transplantation at the UPMC Hillman Cancer Center in Pittsburgh, during a recorded presentation of the data. There were no cases of movement and neurocognitive adverse effects.

Agha noted that one death occurred 100 days after the infusion of cilta-cel due to COVID-19 infection and was assessed as treatment-related by the investigators.

Early and deep responses were observed with a single infusion of cilta-cel in lenalidomide refractory patients with multiple myeloma, who received one-to three prior lines of therapy, he concluded.

The CAR-T cell therapy is being evaluated in other cohorts of the CARTITUDE-2 in earlier line settings, as well as in the phase 3 CARTITUDE-4 study in patients with one to three prior lines of therapy.

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Novel CAR-T Cell Therapy Produces Early and Deep Responses in Certain Patients with Multiple Myeloma - Curetoday.com

Innovent Biologics and IASO Biotherapeutics to Present Updated Data from its Anti-BCMA CAR-T Therapy in Relapsed/Refractory Multiple Myeloma at…

SAN FRANCISCO and SUZHOU, China, June 7, 2021 /PRNewswire/ -- Innovent Biologics Inc. ("Innovent", HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, together with IASO Biotherapeutics (IASO Bio), jointly announced to deliver an oral presentation on updated data from the Phase I study of IBI326 in patients with relapsed/refractory multiple myeloma (R/R MM) at the European Hematology Association (EHA) Congress, June 9-17, 2021. The presentation will further demonstrate the safety, efficacy, and increased persistence of IBI326.

IBI326 is a fully-human B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy co-developed by IASO Bio and Innovent (Innovent: IBI326, IASO Bio: CT103A), and it is currently under the pivotal Phase II clinical trial. In February 2021, IBI326 was granted the Breakthrough Therapy Designation (BTD) by China regulatory authority, National Medical Production Administration (NMPA) for the treatment of relapsed/refractory multiple myeloma.

In the oral presentation, Professor Chunrui Li with Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology (HUST) in China will report the clinical data on 35 patients with R/R MM, who received 1.0, 3.0, or 6.0 106/kg IBI326 treatment respectively in the dose-escalation phase and dose-expansion cohort. The 1.0 106/kg dose was determined as Recommended Phase II Dose (RP2D). The median age of the 35 patients was 54 (27, 72). Among them, eight patients had extramedullary multiple myeloma (EMM) and one patient had complication with plasma cell leukemia. The median number of prior treatment regimens was four (3, 12). Ten patients previously received autologous hematopoietic stem cell transplantation (AHSCT), and 10 patients received murine BCMA CAR-T treatment. As of May 1, 2021, the median follow-up of the 35 patients was 291 days (21, 954).

The clinical data of the study in patients with R/R MM presented at the 61st American Society of Hematology (ASH) Annual Meeting in 2019 highlighted the impressive safety profile, efficacy, and durability of response of IBI326. The study also included four patients who had relapsed after prior murine BCMA CAR T-cell treatment. The overall response of these four patients demonstrated that IBI326 can also be an effective treatment option for patients who have relapsed from a prior CAR-T therapy.

In June 2021, the results were published in Blood, a peer-reviewed journal specializing in hematology, in an article titled "A phase 1 Study of a Novel Fully Human BCMA-targeting CAR (IBI326) in Patients with Relapsed/Refractory Multiple Myeloma." The editors of Blood were impressed by the unique persistence of IBI326 and the authors' exposition on the re-treatment prospects of the disease during the study. Therefore, they invited experts from University College London Cancer Institute to write a review titled "BCMA CARs in multiple myeloma: room for more?" (DOI 10.1182/blood.2021010833).

Dr. Hui Zhou, Senior Vice President of Medical Development, Innovent Biologics, said, "We are glad to see that the excellent clinical data of IBI326 (IASO: CT103aA) has been highly recognized by the EHA congress. In particular, it still shows good clinical benefits to the patients who received prior murine BACM CAR-T treatment, and provides better treatment options for patients with relapsed/refractory multiple myeloma. We look forward to the launch of this cell therapy to benefit patients in the future. "

Maxwell Wang, Chief Executive Officer of IASO Bio, said, "We are very glad that our high-quality clinical data are presented at the European Hematology Association Congress, one of the top global academic conferences. It's also the only oral presentation on a China-developed BCMA CAR-T treatment at this year's EHA Congress. The updated data reinforce the advantages and uniqueness of CT103A in the treatment of patients with relapsed/refractory multiple myeloma. Particularly, we enrolled 8 patients with extramedullary multiple myeloma and 10 patients receiving prior murine BCMA CAR-T treatment. All patients have obtained clinical benefits. IASO Biotherapeutics will continue to leverage its innovative clinical development strategy to further prove the advantages of CT103A. We also look forward to the oral presentation by Professor Chunrui Li with Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology (HUST) at the EHA Congress."

Presentation details:

Abstract: S194 AN UPDATED PHASE 1 STUDY OF A NOVEL FULLY HUMAN BCMA-TARGETING CAR-T CELLS (CT103A) IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA

Type: Oral Presentation

Session title: T cell re-directing therapies in relapsed/refractory multiple myeloma

About Multiple Myeloma

Multiple Myeloma is a deadly blood cancer that often infiltrates the bone marrow causing anemia, kidney failure, immune problems, and bone fractures. For multiple myeloma patients, common first-line drug treatments include proteasome inhibitors, immunomodulatory drugs, and alkylating agents. While treatment may result in remission, most patients will inevitably enter the relapsed or refractory stage as there's currently no cure. As a result, there is a significant unmet need for patients with relapsed/refractory multiple myeloma.

About IBI326 (BCMA CAR-T)

IBI326 is an innovative therapy co-developed by Innovent and IASO Bio. Previous studies indicate subjects with relapsed/refractory multiple myeloma (R/R MM) who received high-dose BCMA-targeting CAR-T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses again, the re-infusion of CAR-T cells will not be effective. To solve this dilemma, IBI326 has been developed, a lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3 activation domains. Based on strict selection and screening, utilizing a proprietary in-house optimization platform, the construct of the BCMA CAR-T is potent and persistent. In February 2021, IBI326 was granted breakthrough therapy designation by the NMPA for the treatment of relapsed/refractory multiple myeloma.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high quality innovative medicines for the treatment of cancer, autoimmune, metabolic diseases, and other major therapeutic areas. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. By leveraging this platform, the company has built a robust pipeline of 24 valuable assets in major therapeutic areas, with 4 products officially approved for marketing in China - TYVYT (sintilimab injection), BYVASDA (bevacizumab biosimilar injection), SULINNO (adalimumab biosimilar injection) and HALPRYZA (rituximab biosimilar injection), one Biologics License Application (BLA)submission for sintilimab accepted by the U.S. FDA, six assets in Phase 3 or pivotal clinical trials, and 14 more molecules in clinical trials. TYVYT (sintilimab injection) was included in the National Reimbursement Drug List (NRDL) in 2019 as the historically first PD-1 inhibitor entering in NRDL and the only PD-1 included in the list in that year.

Innovent has built an international team of advanced talented professionals in high-end biopharmaceutical development and commercialization, including many overseas experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, Hanmi and other international partners. Innovent strives to work with all relevant parties to help advance China's biopharmaceutical industry, improve drug availability to ordinary people and enhance the quality of the patients' lives. For more information, please visit: http://www.innoventbio.com.

About IASO Bio

IASO Bio is a clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and autoimmune diseases. Leveraging its proprietary fully human antibody discovery platform (IMARS), high-throughput CAR-T drug priority platform, and proprietary manufacturing processes, IASO Bio is developing a rich clinical-stage pipeline of multiple autologous and allogeneic CAR-T and biologics product candidates. Currently, the company is developing a diversified portfolio of over 10 novel pipeline products, IASO's leading asset, IBI326, an innovative anti-BCMA CAR-T cell therapy under pivotal study for relapsed/refractory (R/R) multiple myeloma (RRMM), was granted Breakthrough Therapeutic Designation by China's National Medical Products Administration (NMPA) in February 2021. For more information on IASO, please visit http://www.iasobio.com.

Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to the Company, are intended to identify certain of such forward-looking statements. The Company does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of the Company with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond the Company's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, the Company's competitive environment and political, economic, legal and social conditions.

The Company, the Directors and the employees of the Company assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialise or turn out to be incorrect.

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Innovent Biologics and IASO Biotherapeutics to Present Updated Data from its Anti-BCMA CAR-T Therapy in Relapsed/Refractory Multiple Myeloma at...

High Rate of Response Noted in MCL and CLL With Cirmtuzumab Plus Ibrutinib – Cancer Network

Patients with mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) who were treated with cirmtuzumab and ibrutinib (Imbruvica) in a phase 1/2 trial showed promising responses with and tolerability of therapy, according to data presented at the American Society of Clinical Oncology (ASCO) Annual Meeting.

The majority of the patients demonstrated a significant reduction in tumor sizes, lead study author Hun Ju Lee, MD, assistant professor of medicine in the Department of Lymphoma & Myeloma at The University of Texas MD Anderson Cancer Center said during the presentation.

ORR for patients with MCL was 83.3% and was 91.1% for patients with CLL. The complete response rates were 38.9% and 14.7% for the MCL and CLL arms, respectively. Ultimately, 94.4% of patients with MCL and 100% of patients with CLL elicited a clinical benefit from the cirtuzumab/ibrutinib regimen.

The median progression-free survival in both cancers was not reached.

Because MCL and CLL are considered incurable, the study aimed to test the efficacy and safety profile of cirmtuzumab, which inhibits tumor promoting activity of onco-embryonic tyrosine kinase receptor ROR1 found in many solid and hematologic cancers, plus ibrutinib in patients with relapsed/refractory MCL or treatment nave or relapsed/refractory CLL.

The study was performed in 3 parts with separate arms. Part 1, for dose escalation; part 2, for dose expansion; and part 3, comparing cirmtuzumab plus ibrutinib with ibrutinib alone in CLL.

Overall, 26 patients with refractory MCL (median age 66.5, 15.4% women) and 34 patients with treatment nave or RR CLL (median age 68, 23.5% women) were enrolled in the study.

For part 1, 12 patients with MCL were enrolled, and 5 into part 2. The median number of prior regimens was 2, including patients relapsing after ibrutinib (n=4), autologous stem-cell transplantation (n=3), autologous stem cell transplantation/allogenic stem cell transplantation (1) and autologous stem cell transplantation /CAR-T (1). For patients with CLL, at least 74% were high risk, as determined by unmutated IGHV, del17p and/or del11q, in parts 1 and 2.

In part 1, cirmtuzumab was given intravenously 5 times every 2 weeks, and then every 4 weeks, at 2 to 16 mg. Three-hundred or 600 mg doses were also examined. Researchers assessed the safety profile of cirmtuzumab during the first 28 days, which was then followed by ibrutinib at approved doses for each indication. A treatment regimen of cirmtuzumab (600 mg) given intravenously 3 times every 2 weeks, and then every 4 weeks, in combination with ibrutinib starting day 0, was chosen as the recommended dosing for parts 2 and 3.

In summary, cirmtuzumab plus ibrutinib is a very well tolerated regimen, Lee noted.

Adverse events with 20% or greater incidence were recorded, including fatigue (n=11), diarrhea (n = 9), contusion (n = 7), dizziness (n = 7) and nausea (n = 7). The efficacy is robust in many of these pre-treated patients, [including] high response, rate durable response [and] encouraging PFS, demonstrating clinical benefit, he concluded.

Of note, the phase 2 study for CLL is completed, and is awaiting a long-term follow-up. Phase 2 for MCL is currently enrolling.

Reference

Lee HJ, Choi M, Siddiqi T, et al. Phase 1/2 study of cirmtuzumab and ibrutinib in mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL).J Clin Oncol. 2021;39(suppl 15; abstr 7556).

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High Rate of Response Noted in MCL and CLL With Cirmtuzumab Plus Ibrutinib - Cancer Network

Dr. Ghosh on the Role of Off-the-Shelf CAR T-Cell Therapy in Myeloma June – OncLive

Monalisa Ghosh, MD, discusses the role of off-the-shelf CAR T-cell therapy in patients with multiple myeloma.

Monalisa Ghosh, MD, a clinical assistant professor at the University of Michigan, discusses the role of off-the-shelf CAR T-cell therapy in patients with multiple myeloma.

These products are promising in many ways and provide several advantages, including a decreased manufacturing time, Ghosh says. Experts in the field can request and receive off-the-shelf CAR T-cell products from a bank, she explains.This eliminates the need to wait for patient cell collection, which puts the patient at some degree of risk, and decreases the manufacturing time that ordinarily takes several weeks. The decreased treatment timeline can also be beneficial to patients with rapidly progressive disease, Ghosh notes.

However, challenges exist with this therapy, as allogenic cells may cause certain adverse effects, such as a graft-versus-host reaction that is similar to reactions observed with stem cell transplantation, Ghosh says. Currently, certain methods of T-cell receptor engineering may be able to mitigate this risk, she adds.Additionally, some hosts may reject the cells, a possibility that has been observed in early studies, wherein cells have not demonstrated long-term persistence.It may be possible to overcome this through multiple cell infusions, Ghosh notes.

Overall, the accessibility of off-the-shelf CAR T-cell products to a large group of patients with multiple myeloma appears promising, Ghosh concludes.

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Dr. Ghosh on the Role of Off-the-Shelf CAR T-Cell Therapy in Myeloma June - OncLive

Triplet Combo of Polatuzumab Vedotin, Rituximab and Lenalidomide Safe, Effective to Treat Relapsed/Refractory DLBCL – Cancer Network

The novel triplet combination with polatuzumab vedotin (Polivy), rituximab, and lenalidomide was safe while improving overall and complete responses for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to data presented at the 2021 ASCO Annual Meeting.

In this first report of a triplet combination of polatuzumab, rituximab and lenalidomide, the triplet combination showed notable efficacy in a challenging-to-treat relapsed and refractory diffuse large B-cell lymphoma population, said Catherine S.M. Diefenbach, MD, associate professor of medicine, translational director of hematology and director of clinical lymphoma at Perlmutter Cancer Center at NYU Langone Health, during the virtual presentation.

In this phase 1b/2 trial, researchers analyzed the safety of this combination in 57 patients (median age, 71 years; 67% men) with relapsed/refractory diffuse large B-cell lymphoma, were ineligible for or failed prior autologous stem cell transplantation and were treated with at least one prior anti-CD20-containing chemo-immunotherapy regimen. Efficacy of the treatment was assessed in 49 patients (median age, 72 years; 63% men).

The median age was 71, as is typical for this lymphoma, but the age range was from between 28 and 92 years, Diefenbach said.

Most patients in the safety and efficacy groups (86% and 84%, respectively) had stage 3 to 4 disease, nearly a quarter had two lines of therapy (28% and 27%) and nearly a third had three or more lines of therapy (33% and 31%). In addition, some patients underwent previous CAR T-cell therapy (5% and 6%, respectively) or prior bone marrow transplant (11% and 12%).

At induction, all patients received induction during 6 28-day cycles with 1.8 mg/kg of intravenous polatuzumab vedotin, 375 mg/m2 of intravenous rituximab and either a dose escalation of oral lenalidomide (between 10 mg and 20 mg) or the recommended daily dose of the drug on days 1 through 21. Patients who responded to the treatment at the end of induction received 6 months consolidation of 10 mg of lenalidomide (days 1 through 21, monthly) and 375 mg/m2 of rituximab (day 1 every 2 months).

Primary endpoints for this trial included the safety and tolerability of this triplet combination, in addition to complete response rates at the end of induction as assessed by positron emission tomography (PET) scans. Follow-up was conducted for a median of 9.7 months in the safety population and for 9.5 months in the efficacy population.

In the safety population, 75% of patients experienced grade 3 to 4 adverse events, with the most common including neutropenia (58%), thrombocytopenia (14%) and infections (14%). Adverse events led to 26% of patients undergoing a lenalidomide dose reduction and 67% had treatment interruption. One grade 5 adverse event related to the treatment neutropenic sepsis was reported.

The additional (adverse events) were not considered related to study drug, Diefenbach said. For example, a patient who had a fatal gastric hemorrhage who had been enrolled but not yet treated, and a patient with COVID-19 who contracted this disease 167 days after his last dose of the study therapy.

In the efficacy population, the overall response rate was 39% with a complete response rate of 29%. Ten percent of patients had a partial response. Median progression-free survival for the entire population was 6.3 months (95% CI, 4.5-9.7) with a median duration of remission of 8.1 months (95% CI, 4.7-not evaluated) and a median overall survival of 10.9 months (95% CI, 10.9-not evaluated).

However, for the patients who obtained a (complete response) this is 13 patients who were evaluable, the median progression-free survival at 9 months had not been reached, nor has the median overall survival, Diefenbach said. Nearly all patients remain in complete remission.

Additional follow-up is needed to assess the impact of consolidation therapy on the duration of long-term response, Diefenbach said. In summary, the triplet combination of polatuzumab, rituximab and lenalidomide represents a potential novel regimen for patients with transplant-ineligible relapsed and refractory diffuse large B-cell lymphoma and is worthy of further study.

Reference

Magid Diefenbach CS, Abrisqueta P, Gonzalez-Barca E, et al. Polatuzumab vedotin (Pola) + rituximab (R) + lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Primary analysis of a phase 1b/2 trial. J Clin Oncol. 2021;39(suppl 15):Abstract 7512.

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Triplet Combo of Polatuzumab Vedotin, Rituximab and Lenalidomide Safe, Effective to Treat Relapsed/Refractory DLBCL - Cancer Network

Income, Education Affect Treatment and Survival in MDS – DocWire News

There may be a correlation between income and education and treatment and survival among patients with myelodysplastic syndromes (MDS), according to a study. The results were published in the European Journal of Haematology.

Using the Swedish MDS Register, the researchers identified 2,945 patients diagnosed with MDS between 2009 and 2018. They evaluated relative mortality using Cox regression and treatment differences using Poisson regression. Mortality comparisons were made using a matched group from the general population.

Patients in the lowest income category, compared to the highest, had 50% higher mortality; similarly, those with mandatory school education had 40% higher mortality than those with college or university education. There were also correlations observed between treatment with hypomethylating agents and allogeneic stem cell transplantation (SCT), and investigation with cytogenetic diagnostics, and income and education. Differences in risk class or comorbidity at the time of diagnosis did not account for these differences in mortality and treatment.

In this large, population-based study, we demonstrate that Swedish MDS patients with lower income or shorter education have shorter survival. They are further less likely to be investigated with cytogenetic diagnostics, and less likely to receive treatment with hypomethylating agents, or an allogeneic SCTthe only existing curative treatment for MDS today, the researchers wrote in their conclusion.

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Income, Education Affect Treatment and Survival in MDS - DocWire News

Polatuzumab With Rituximab and Lenalidomide Shown Safe and Effective for Relapsed/Refractory DLBCL – Targeted Oncology

In patients with relapsed/refractory diffuse large B-cell lymphoma treated with the triplet combinaton of polatuzumab vedotin (Polivy), rituximab and lenalidomide, therapy was considered to be safe and effective, according to data presented at the 2021 ASCO Annual Meeting.

In this first report of a triplet combination of polatuzumab, rituximab and lenalidomide, the triplet combination showed notable efficacy in a challenging-to-treat relapsed and refractory diffuse large B-cell lymphoma population, said Catherine S.M. Diefenbach, MD, associate professor of medicine, translational director of hematology and director of clinical lymphoma at Perlmutter Cancer Center at NYU Langone Health, during the virtual presentation.

In this phase 1b/2 trial, researchers analyzed the safety of this combination in 57 patients (median age, 71 years; 67% men) with relapsed/refractory diffuse large B-cell lymphoma, were ineligible for or failed prior autologous stem cell transplantation and were treated with at least one prior anti-CD20-containing chemo-immunotherapy regimen. Efficacy of the treatment was assessed in 49 patients (median age, 72 years; 63% men).

The median age was 71, as is typical for this lymphoma, but the age range was from between 28 and 92 years, Diefenbach said.

Most patients in the safety and efficacy groups (86% and 84%, respectively) had stage 3 to 4 disease, nearly a quarter had two lines of therapy (28% and 27%) and nearly a third had three or more lines of therapy (33% and 31%). In addition, some patients underwent previous CAR T-cell therapy (5% and 6%, respectively) or prior bone marrow transplant (11% and 12%).

At induction, all patients received induction during 6 28-day cycles with 1.8 mg/kg of intravenous polatuzumab vedotin, 375 mg/m2 of intravenous rituximab and either a dose escalation of oral lenalidomide (between 10 mg and 20 mg) or the recommended daily dose of the drug on days 1 through 21. Patients who responded to the treatment at the end of induction received 6 months consolidation of 10 mg of lenalidomide (days 1 through 21, monthly) and 375 mg/m2 of rituximab (day 1 every 2 months).

Primary endpoints for this trial included the safety and tolerability of this triplet combination, in addition to complete response rates at the end of induction as assessed by positron emission tomography (PET) scans. Follow-up was conducted for a median of 9.7 months in the safety population and for 9.5 months in the efficacy population.

In the safety population, 75% of patients experienced grade 3 to 4 adverse events, with the most common including neutropenia (58%), thrombocytopenia (14%) and infections (14%). Adverse events led to 26% of patients undergoing a lenalidomide dose reduction and 67% had treatment interruption. One grade 5 adverse event related to the treatment neutropenic sepsis was reported.

The additional (adverse events) were not considered related to study drug, Diefenbach said. For example, a patient who had a fatal gastric hemorrhage who had been enrolled but not yet treated, and a patient with COVID-19 who contracted this disease 167 days after his last dose of the study therapy.

In the efficacy population, the overall response rate was 39% with a complete response rate of 29%. Ten percent of patients had a partial response. Median progression-free survival for the entire population was 6.3 months (95% CI, 4.5-9.7) with a median duration of remission of 8.1 months (95% CI, 4.7-not evaluated) and a median overall survival of 10.9 months (95% CI, 10.9-not evaluated).

However, for the patients who obtained a (complete response) this is 13 patients who were evaluable, the median progression-free survival at 9 months had not been reached, nor has the median overall survival, Diefenbach said. Nearly all patients remain in complete remission.

Additional follow-up is needed to assess the impact of consolidation therapy on the duration of long-term response, Diefenbach said. In summary, the triplet combination of polatuzumab, rituximab and lenalidomide represents a potential novel regimen for patients with transplant-ineligible relapsed and refractory diffuse large B-cell lymphoma and is worthy of further study.

Reference

Magid Diefenbach CS, Abrisqueta P, Gonzalez-Barca E, et al. Polatuzumab vedotin (Pola) + rituximab (R) + lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Primary analysis of a phase 1b/2 trial. J Clin Oncol. 2021;39(suppl 15):Abstract 7512.

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Polatuzumab With Rituximab and Lenalidomide Shown Safe and Effective for Relapsed/Refractory DLBCL - Targeted Oncology

Early Promise Observed With Lisaftoclax in Relapsed/Refractory CLL and Other Hematologic Malignancies – Targeted Oncology

Lisaftoclax (APG-2575), a novel BCL-2 inhibitor, has demonstrated encouraging responses with acceptable safety in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), and other hematologic cancers who were treated in first-in-human phase 1 trial (NCT03537482), according to data presented during the 2021 ASCO Annual Meeting.1

Twelve of 15 evaluable patients with relapsed/refractory CLL/SLL experienced a partial response (PR) to treatment with lisaftoclax, which translated to an objective response rate (ORR) of 80%. In this population, the median number of treatment cycles was 9 (range, 5-24) and the median time to response was 2 cycles (range, 2-8).

Moreover, the BCL-2 inhibitor was also administered to 21 patients with nonCLL/SLL malignancies, which included those with non-Hodgkin lymphoma (NHL; n = 12), multiple myeloma (n = 6), myeloid malignancies (n = 2), and hairy cell leukemia (n = 1). The median duration of treatment in these patients was 3 cycles (range, 1-22). None of these patients were found to achieve a PR or better with lisaftoclax, although 1 patient with multiple myeloma and t(11;14) experienced a minor response to treatment.

Importantly, no dose-limiting toxicities (DLTs) were observed with the agent, even when administered at the highest dose of 1200 mg.

[Lisaftoclax] is a very well-tolerated agent, even up to doses of 1200 mg and has infrequent grade 3 or 4 treatment-related adverse effects [TRAEs]. No tumor lysis syndrome [TLS] or DLT was observed and the maximum-tolerated dose [MTD] has not been reached, Sikander Ailawadhi, MD, lead study author, consultant and professor of medicine, Department of Medicine, in the Division of Hematology/Oncology, at Mayo Clinic, said during a presentation on the data. Our preliminary data suggest proof of concept, with an ORR of 80% in patients with relapsed/refractory CLL or SLL.

Lisaftoclax is a novel, potent, orally active, selective BCL-2 inhibitor that is currently under development. By targeting the antiapoptotic BCL-2 family of proteins, the agent serves to prevent cancer cells from circumventing apoptosis, which would allow for extended survival. Notably, many hematologic malignancies are characterized by having high levels of BCL-2.

Although another BCL-2 inhibitor, venetoclax (Venclexta), has been FDA approved in this space, the agent has been linked with TLS; thus, the agent requires a 5-week ramp-up. Moreover, venetoclax has been found to be associated with other AEs, such as thrombocytopenia and severe neutropenia.2

Previously, in preclinical models of B-cell malignancies, lisaftoclax has proven to be able to selectively target BCL-2 and to demonstrate antitumor activity. When the cell-free kinetics of the agent was compared with venetoclax, the agents appeared to showcase a similar profile, according to Ailawadhi. In a cell line of acute lymphoblastic leukemia, which is BCL-2 driven, selectivity for BCL-2 was again demonstrated by lisaftoclax. Other models have demonstrated that the mechanism of action of the agent allows it to disrupt the BCL-2:BIM complex, which mediates the induction of apoptosis.

In the phase 1 study, investigators set out to evaluate oral lisaftoclax at daily doses ranging from 20 mg to 1200 mg in a 28-day treatment cycle. The clinical trial initially included an accelerated dose escalation with 1 or more patients per dose level.

However, once the dose level reached 400 mg, a DLT was observed, any laboratory or clinical TLS was observed, any hypersensitivity reaction was suspected, 2 grade 2 drug-related toxicities, or 1 or more grade 3 drug-related toxicities were reported, the standard 3+3 dose-escalation design would begin.

At that time, patients were then divided into 1 of 2 cohorts. Patients enrolled to cohort A had non-CLL hematologic malignancies and low risk of TLS, while those enrolled to cohort B had CLL or another hematologic malignancy with intermediate/high risk of TLS. Three to 6 patients were treated per dose level.

Once the MTD was reached or the recommended phase 2 dose (RP2D) was determined, then the dose-expansion phase of the study would begin. Patients received treatment until either progressive disease or intolerable toxicity.

The objectives of the early-phase trial are to examine safety in the form of DLTs, MTD, and RP2D, as well as to characterize the pharmacokinetic (PK) profile of the agent and its efficacy. Key efficacy end points include ORR, progression-free survival, duration of response, overall survival, and minimal residual disease status.

To be eligible for enrollment, patients needed to have histologically confirmed relapsed/refractory CLL/SLL, multiple myeloma, Waldenstrm macroglobulinemia, myeloid malignancies, and NHL, which included diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Patients also needed to have acceptable hematologic and renal function.

If patients had previously received treatment with a BCL-2 inhibitor; had undergone allogeneic hematopoietic stem cell transplant within 1 year; had Burkitt lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukemia; or required concurrent central nervous system therapy, they were excluded.

At the time of the April 15, 2021, data cutoff, a total of 36 patients had been enrolled to the trial. The median age of study participants was 70.0 years (range, 39-89), with 52.8% of patients aged 70 years or older. The majority of patients were male (72.2%) and had a median number of 2 prior therapies (range, 1-13).

Moreover, 58.3% (n = 21) of patients have discontinued treatment, and the most frequently cited reason was because of disease progression (61.9%; n = 13). Other reasons for discontinuation included toxicity (9.5%), patient withdrawal (14.3%), or physician decision (14.3%). One patient was switched to a standard-of-care regimen because of symptomatic anemia, 1 was switched to another option because of hepatitis B reactivation, and 1 was switched to another option because of lack of response to treatment.

The swimmer plot also showed a couple of things of prominence. One, there is a significant proportion of patients who are ongoing on treatment, Ailawadhi noted. Also, youll especially notice in [patients with] CLL, early on, the presence of PRs. A significant number of patients at various dose levels achieved a PReven at the 2-cycle mark. This was something quite prominent and [says something] about the efficacy of the drug.

When looking specifically at patients with non-CLL/SLL malignancies, the clinical benefit rate (CBR) achieved with lisaftoclax was 50.0% (n = 10). Specifically, in those with NHL, multiple myeloma, myeloid malignancy, and hairy cell leukemia, these rates were 63.6% (n = 7), 40.0% (n = 2), 0%, and 100% (n = 1), respectively.

Five of these 21 patients were treated at a dose below 600 mg, Ailawadhi said. Even in these patients, with the single-agent treatment, half the patients had stable disease. This is, in fact, encouraging and warrants further focused development within these disease areas.

When looking at the patients in the CLL/SLL group (n = 15), 14 patients had CLL, and 1 patient had SLL. Moreover, within this subset, 53.3% of patients had stage I to II disease, while 46.7% had stage III or IV disease. When looking at the International Prognostic Index for CLL, 20% of patients were low, 33.3% were intermediate, 40% were high, and 6.7% were very high.

Additionally, 2 patients had del(17p)/TP53 mutation, 1 had del(11q), 3 had CD38 positivity, and 9 patients had unmutated IgVH. All patients previously received CD20 antibody-based therapy, 2 received prior fludarabine, and 4 had prior BTK inhibition. Four patients had bulky disease.

Focusing just on the efficacy within the [patients with] CLL/SLL, we can see a bit more clearly that a lot of patients are still continuing therapyespecially on higher doses, Ailawadhi said. Several patients achieved PR, even early on in their treatment.

Overall, the safety profile of lisaftoclax was found to be favorable. Any-grade treatment-related AEs (TRAEs) were reported in 75% of patients, and these included fatigue (27.8%), neutropenia (22.2%), diarrhea (19.4%), anemia (16.7%), constipation (11.1%), and nausea (11.1%). Grade 3 or higher TRAEswhich occurred in 5% or more of patientswere experienced by 25% of patients and included neutropenia (13.9%), nausea (5.6%), and decreased platelet count (5.6%).

Only 1 patient discontinued treatment with lisaftoclax because of a TRAE, which was grade 2 pruritus and skin sensitivity. Notably, no grade 5 TRAEs were observed.

The MTD was not reached, and no laboratory or clinical TLS has been reported. Itis quite a prominent finding that no TLS was noted in any of the patients on any of the cohorts during the study, at any of those dose levels, Ailawadhi said. In cohort B, which is the high-risk TLS group, 600 mg of [lisaftoclax] has been selected as the RP2D based on the clinical results and the PK/pharmacodynamic profile. In cohort A, there is still 1 slot to be enrolled at the 1200-mg dose after which the RP2D will be determined.

The preliminary PK profile of the agent demonstrated that exposures increased with doses from 20 mg to 1200 mg, with an average half-life ranging from 4 to 8 hours. So, there was some activity at lower doses, as well, Ailawadhi noted.

Additionally, on BH3 profiling, the drug was found to rapidly trigger complex changings in BCL-2 proteins among samples collected from patients with CLL/SLL; these changes were consistent with rapid clinical reductions in absolute lymphocyte counts.

[Lisaftoclax, based on all of these data, holds very good promise as a potential treatment alternative for patients with relapsed/refractory CLL, SLL, or other hematologic malignancies where BCL-2 may be a driver with a significantly shorter daily ramp-up schedule, as against weekly, and a very favorable safety profile based on these data, Ailawadhi concluded.

References

1. Ailawadhi S, Chanan-Khan AAA, Chen Z, et al. First-in-human study of lisaftoclax (APG-2575), a novel BCL-2 inhibitor (BCL-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs). J Clin Oncol. 2021;39(suppl 15):7502. doi:10.1200/JCO.2021.39.15_suppl.7502

2. Davids MS, Hallek M, Wierda W, et al. Comprehensive safety analysis of venetoclax monotherapy for patients with relapsed/refractory chronic lymphocytic leukemia. Clin Cancer Res. 2018;24(18):4371-4379. doi:10.1158/1078-0432.CCR-17-3761

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Early Promise Observed With Lisaftoclax in Relapsed/Refractory CLL and Other Hematologic Malignancies - Targeted Oncology

Mustang Bio to Host Key Opinion Leader Webinar on MB-106 CD20-Targeted CAR T for – GlobeNewswire

Webinar to be held Tuesday, June 15, 2021, at 1:00 p.m. ET

WORCESTER, Mass., June 07, 2021 (GLOBE NEWSWIRE) -- Mustang Bio, Inc. (Mustang) (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, today announced that it will host a key opinion leader (KOL) webinar on MB-106 CD20-targeted CAR T cell therapy, which is being developed for high-risk B-cell non-Hodgkin lymphomas (B-NHL) and chronic lymphocytic leukemia (CLL), on Tuesday, June 15, 2021, at 1:00 p.m. Eastern Time.

The webinar will feature a presentation by Mazyar Shadman, M.D., M.P.H., Associate Professor at the Fred Hutchinson Cancer Research Center (Fred Hutch), who will discuss interim results from the ongoing Phase 1/2 clinical trial investigating the safety and efficacy of MB-106 CD20-targeted CAR T for B-NHL and CLL. These data have been selected for an e-poster presentation at the European Hematology Association 2021 Virtual Congress (EHA2021), which is being held June 9-17. Dr. Shadman, along with colleague Brian Till, M.D., also an Associate Professor at Fred Hutch, will be available to answer questions following the formal presentations.

Mustangs management team will also provide more details on the planned MB-106 Phase 1/2 clinical trial to be conducted under Mustangs Investigational New Drug (IND) application. The Company recently announced that the U.S. Food and Drug Administration (FDA) accepted its IND to initiate a multicenter Phase 1/2 clinical trial investigating the safety, tolerability and efficacy of MB-106 for relapsed or refractory B-NHL and CLL.

To participate in the webinar, please register here.

About Dr. Shadman Mazyar Shadman, M.D., M.P.H., is an Associate Professor at the University of Washington (UW) and Fred Hutch. He is a hematologic malignancies expert who specializes in treating patients with lymphoma and CLL. Dr. Shadman is involved in clinical trials using novel therapeutic agents, immunotherapy (CAR T cells), and stem cell transplant for treatment of lymphoid malignancies with a focus on CLL. He also studies the clinical outcomes of patients using institutional and collaborative retrospective cohort studies.

Dr. Shadman received his M.D. from Tehran University in Iran. He finished an internal medicine internship and residency training at the Cleveland Clinic in Cleveland, Ohio. He completed his fellowship training in hematology and medical oncology at UW and Fred Hutch. Dr. Shadman also earned an M.P.H. degree from UW and was a fellow for the National Cancer Institutes cancer research training program at Fred Hutch, where he studied cancer epidemiology.

About Dr. Till Brian Till, M.D., is an Associate Professor in the Clinical Research Division of Fred Hutch and Department of Medicine at UW. His laboratory focuses on developing chimeric antigen receptor (CAR)-based immunotherapies for non-Hodgkin lymphoma and understanding why CAR T cell therapies work for some patients but not for others. He led the first published clinical trial testing CAR T cells as a treatment for lymphoma patients. Dr. Till also has a clinical practice treating patients with lymphoma and attends on the stem cell transplantation and immunotherapy services at the Seattle Cancer Care Alliance.

About Mustang Bio Mustang Bio, Inc. is a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases. Mustang aims to acquire rights to these technologies by licensing or otherwise acquiring an ownership interest, to fund research and development, and to outlicense or bring the technologies to market. Mustang has partnered with top medical institutions to advance the development of CAR T therapies across multiple cancers, as well as a lentiviral gene therapy for X-linked severe combined immunodeficiency. Mustang is registered under the Securities Exchange Act of 1934, as amended, and files periodic reports with the U.S. Securities and Exchange Commission (SEC). Mustang was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visit http://www.mustangbio.com.

ForwardLooking Statements This press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under, and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; risks relating to the timing of starting and completing clinical trials; uncertainties relating to preclinical and clinical testing; our dependence on third-party suppliers; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995.

Company Contacts: Jaclyn Jaffe and Bill Begien Mustang Bio, Inc. (781) 652-4500 ir@mustangbio.com

Investor Relations Contact: Daniel Ferry LifeSci Advisors, LLC (617) 430-7576 daniel@lifesciadvisors.com

Media Relations Contact: Tony Plohoros 6 Degrees (908) 591-2839 tplohoros@6degreespr.com

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Mustang Bio to Host Key Opinion Leader Webinar on MB-106 CD20-Targeted CAR T for - GlobeNewswire