On June 1, 2022 Gamida Cell Ltd. (Nasdaq: GMDA), the leader in the development of NAM-enabled cell therapy candidates for patients with hematologic and solid cancers and other serious diseases, reported the activation of the initial clinical sites to screen and enroll patients in the company-sponsored Phase 1/2 study evaluating a cryopreserved formulation of GDA-201, a readily available cell therapy candidate for the treatment of follicular and diffuse large B cell lymphomas (NCT05296525) (Press release, Gamida Cell, JUN 1, 2022, View Source [SID1234615381]). On April 26, 2022, Gamida had announced that the U.S. Food and Drug Administration (FDA) cleared its investigational new drug (IND) application and removed the clinical hold for a cryopreserved formulation of GDA-201.

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"We are excited to be screening patients for enrollment in our company-sponsored Phase 1/2 clinical study of our novel, cryopreserved formulation of GDA-201, which has the potential to address the significant unmet need that exists for patients with follicular and diffuse large B cell lymphomas having relapsed or refractory disease," said Ronit Simantov, M.D., chief medical and scientific officer of Gamida Cell. "As described in previously announced clinical data, an investigator-sponsored (IS) study evaluating the fresh formulation of GDA-201 demonstrated encouraging results in heavily pretreated patients with lymphoma. With the initiation of enrollment, we look forward to dosing the first patient in our clinical study of the novel cryopreserved formulation of GDA-201."

GDA-201 leverages Gamida Cell’s proprietary NAM technology platform to expand the number and functionality of NK cells to direct tumor cell killing properties and antibody-dependent cellular cytotoxicity (ADCC). In an investigator-sponsored Phase 1/2 study in patients with relapsed or refractory lymphoma, treatment with the fresh formulation of GDA-201 with rituximab demonstrated significant clinical activity. Of the 19 patients with non-Hodgkin lymphoma (NHL), 13 complete responses and one partial response were observed, with an overall response rate of 74% and a complete response rate of 68%. The most common Grade 3/4 adverse events were thrombocytopenia, hypertension, neutropenia, febrile neutropenia, and anemia. At the December 2021 Annual Meeting of American Society of Hematology (ASH) (Free ASH Whitepaper), two-year follow-up data were reported on outcomes and cytokine biomarkers associated with survival. The data demonstrated a median duration of response of 16 months (range 5-36 months) and an overall survival at two years of 78% (95% CI, 51%–91%). In the IS study, GDA-201 was well-tolerated and no dose-limiting toxicities were observed in 19 patients with NHL and 16 patients with multiple myeloma.

The study of the cryopreserved formulation of GDA-201 is currently open to enrollment at Henry Ford Health (Detroit, MI) and the Masonic Cancer Center at the University of Minnesota; additional sites will be added in the coming months and updated in Clinicaltrials.gov (NCT05296525). The Phase 1 portion of the study is designed to evaluate the safety of GDA-201 in patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL)/high grade B-cell lymphoma (HGBCL), marginal zone lymphoma or mantle cell lymphoma. The Phase 2 expansion phase is designed to evaluate the safety and efficacy of GDA-201 in two patient cohorts, FL and DLBCL/HGBCL. The study will include patients who have relapsed or refractory lymphoma after at least two prior treatments, which may include CAR-T or stem cell transplant.

About NAM Technology

Our NAM-enabling technology, supported by positive Phase 3 data, is designed to enhance the number and functionality of targeted cells, enabling us to pursue a curative approach that moves beyond what is possible with existing therapies. Leveraging the unique properties of NAM (nicotinamide), we can expand and metabolically modulate multiple cell types — including stem cells and natural killer cells — with appropriate growth factors to maintain the cells’ active phenotype and enhance potency. Additionally, our NAM technology improves the metabolic fitness of cells, allowing for continued activity throughout the expansion process.

About GDA-201

Gamida Cell applied the capabilities of its nicotinamide (NAM)-enabled cell expansion technology to develop GDA-201, an innate NK cell immunotherapy candidate for the treatment of hematologic and solid tumors in combination with standard of care antibody therapies. GDA-201, the lead candidate in the NAM-enabled NK cell pipeline, has demonstrated promising initial clinical trial results. GDA-201 addresses key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs. Furthermore, GDA-201 improves antibody-dependent cellular cytotoxicity (ADCC) and tumor targeting of NK cells. There are approximately 40,000 patients with relapsed/refractory lymphoma in the US and EU, which is the patient population that will be studied in the GDA-201 Phase 1/2 clinical trial.

For more information about GDA-201, please visit View Source For more information on the Phase 1/2 clinical trial of GDA-201, please visit www.clinicaltrials.gov.

GDA-201 is an investigational therapy, and its safety and efficacy have not been established by the FDA or any other health authority.

On June 1, 2022 Seres Therapeutics, Inc. (Nasdaq: MCRB), a leading microbiome therapeutics company, reported the presentation of preclinical data supporting further investigation of a rationally designed microbial consortium candidate (DE486) to prevent or treat gastrointestinal (GI) mucositis – a common and often painful complication of radiation and chemotherapy involving the breakdown of the rapidly-dividing epithelial cells lining the GI tract (Press release, Seres Therapeutics, JUN 1, 2022, businesswire.com/news/home/20220601005127/en/Seres-Therapeutics-Presents-Microbiome-Therapeutic-Research-at-the-2022-American-Society-of-Clinical-Oncology-ASCO-Annual-Meeting [SID1234615380]). These results are available online as part of the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"Microbiome-based therapeutics may offer a potentially novel approach to mitigate debilitating side-effects that can lead to delays or dose reductions of life-saving cancer treatments," said Matthew Henn, Ph.D., Chief Scientific Officer at Seres. "This microbial consortium builds on our scientific and clinical data, and we are encouraged by these preclinical results that suggest potential areas of investigation and future development opportunities for this new area of medicine."

In laboratory experiments, chemotherapy caused mice to develop mucositis of the small intestine and rapidly lose weight. Treatment with a defined consortium of microbes from Seres’ proprietary strain library was shown to reduce inflammation and restore the mice to their normal weight after about a week. In contrast, treating mice with a different microbial cocktail that was intentionally selected to include pro-inflammatory bacteria that may be found in cancer patients with a disrupted microbiome was observed to have the opposite effect, resulting in continued weight loss.

These data support the potential of specifically designed combinations of microbes to minimize damage done to the lining of the GI tract by cancer treatment as a strategy to prevent or manage GI mucositis.

Seres will also present a poster on June 4 at 8:00-11:00 AM CDT detailing the design of an early Phase 1b trial evaluating the efficacy, safety and pharmacokinetics of SER-155 in adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT). SER-155 is a cultivated investigational microbiome therapeutic rationally designed to improve clinical outcomes in patients undergoing HSCT by restoring colonization resistance to pathobionts, promoting epithelial barrier integrity, and reducing colonic inflammation. In addition to SER-109, SER-155 represents Seres’ second active development program in its Infection Protection franchise.

Another poster presentation on June 4 at 1:15-4:15 PM CDT will reprise Phase III trial results of SER-109, an investigational microbiome therapeutic for recurrent C. difficile infection (rCDI). The data showed SER-109 was associated with lower recurrence rate vs. placebo regardless of baseline comorbidity score category. This suggests SER-109 has a side effect profile comparable to placebo and may significantly reduce rCDI rates, which disproportionately affect cancer patients.

Phase 1b Study of SER-155 in Stem Cell Transplant

Hematopoietic stem cell transplant (HSCT) is frequently used to treat lymphoma, leukemia and multiple myeloma or for people who received high doses of chemotherapy or radiation that damaged their bone marrow. While it can be curative, stem cell transplant also carries the risk of life-threatening complications.

A Phase 1b clinical trial (NCT04995653) is now enrolling adults undergoing allogeneic HSCT to test whether the investigational microbiome therapeutic SER-155 is safe and effective at preventing graft-versus-host disease, blood infections and other serious complications.

The trial is designed to enroll 10 participants in an initial open-label cohort to gauge safety. Then, an additional 60 adults will be enrolled into a double-blind, randomized, placebo-controlled arm to assess efficacy. Participants in the second cohort will receive either vancomycin followed by SER-155 or placebo. Adverse events and microbiome samples will be logged for the first year following stem cell transplantation.

Phase 3 ECOSPOR III Study of SER-109 Data Encore

Cancer patients are at greater risk of developing rCDI and tend to have worse outcomes, due to their weakened immune system and frequent antibiotics exposure.i

Encore data from the completed double-blind, randomized, placebo-controlled Phase 3 ECOSPOR III trial (NCT03183128) show that the investigational microbiome therapeutic SER-109 significantly reduced rCDI rates. SER-109 was also observed to be well tolerated, with a safety profile comparable to placebo and no serious drug-related adverse events observed. From 4 weeks post-treatment through 24 weeks, adults with a history of rCDI had fewer recurrences after taking SER-109 compared with those who received placebo.

Seres expects to finalize a Biologics License Application (BLA) submission for SER-109 with the U.S. Food and Drug Administration (FDA) in mid-2022, with an anticipated launch in the first half of 2023, if approved. SER-109 has obtained FDA Breakthrough Therapy and Orphan Drug Designations, supporting the expectation of an expedited review timeline.

About SER-155
SER-155, an oral consortium of cultivated bacteria, is a microbiome therapeutic candidate in clinical development. SER-155 is designed using microbiome biomarker data from human clinical data, human cell-based assays, and in vivo disease models, with the aim to decrease infection and translocation of antibiotic-resistant bacteria in the gastrointestinal tract and modulate host immune responses to decrease GvHD. The rationale for this program is based in part on published clinical evidence from Seres’ collaborators at Memorial Sloan Kettering Cancer Center showing that allogeneic HSCT patients with decreased diversity of commensal microbes are significantly more likely to die due to infection and/or lethal GvHD. SER-155 was developed using Seres’ reverse translational discovery platform to potentially reduce incidences of gastrointestinal infections, bloodstream infections and GvHD in immunocompromised patients, including in patients receiving allogeneic HSCT or solid organ transplants.

About SER-109
SER-109 is an oral microbiome therapeutic candidate consisting of a consortium of highly purified Firmicutes spores, which normally live in a healthy microbiome. SER-109 is designed to prevent the recurrence of CDI by restructuring the microbiome to a state that resists C. difficile colonization and growth. The SER-109 manufacturing purification process is designed to remove unwanted microbes, thereby reducing the risk of pathogen transmission beyond donor screening alone. The FDA has granted SER-109 Breakthrough Therapy designation and Orphan Drug designation for the prevention of rCDI.

On June 1, 2022 AVM Biotechnology, reported that its abstract, "The effects of AVM0703 mobilization of endogenous gamma delta invariant TCR+ bi-specific Natural Killer T-like cells against solid tumors and blood cancers" has been accepted for a poster presentation at the 2022 ASCO (Free ASCO Whitepaper) (American Society of Clinical Oncology) Annual Meeting in Chicago (Press release, AVM Biotechnology, JUN 1, 2022, View Source [SID1234615379]). Founder and CSO, Dr. Theresa Deisher, will present this research on Sunday, June 5th, 2022, in the Developmental Therapeutics – Immunotherapy tract.

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The ASCO (Free ASCO Whitepaper) Annual Meeting showcases cutting-edge research in clinical oncology and is the most influential and prominent scientific gathering of the clinical oncology community.

The chosen abstract concluded that AVM0703 led to:

i) complete response in 27% of immune-resistant mouse A20 tumors as monotherapy and complete response in 60% when combined with 2 doses of cyclophosphamide/fludarabine (CyFlu);

ii) tumor eradication and long-term memory against xenografted human T-cell Acute Lymphoblastic Leukemia (T-ALL);

iii) enhancement of Adoptive Cell Therapy equivalent to CyFlu preconditioning in mouse melanoma; and

iv) preliminary 95% complete response against mouse multiple myeloma.

A second abstract, "Acute supra-pharmacologic weight-based dexamethasone (AVM0703), 18 mgs/kg body weight, mobilizes endogenous bi-specific Natural Killer T-like cells independent of glucocorticoid receptor activation", was chosen for print and online publication.

The acceptance of both abstracts further validates the potential of AVM0703 which is the subject of an ongoing adaptive design expansion cohort clinical trial treating relapsed refractory "no-option" Non-Hodgkin’s Lymphoma/Leukemia. The company is finalizing the dose escalation portion of the trial with positive results including 80% of dosed patients experiencing clinical benefit/immune status improvement and 60% of patients achieving a durable response. Notably, a Peripheral T-cell Lymphoma (PTCL) patient has experienced a durable response with stable disease for 9 months, demonstrating enormous potential for peripheral T-cell lymphoma. The efficacy portion of the trial is anticipated to begin next month.

AVM0703 mobilizes endogenous bi-specific gamma delta TCR+ invariant TCR+ Natural Killer T-like cells resulting in cancer death within hours of administration. The small molecule offers key advantages in the crowded gamma delta field in that these cells are mobilized in vivo avoiding the manufacturing expense and risks of other cell therapies. AVM0703 may be offered as a monotherapy or in combination with chemotherapy or CAR-T and has indications in autoimmune diseases as well as cancer.

Links to the complete abstracts are as follows:

The effects of AVM0703 mobilization of endogenous gamma delta invariant TCR+ bi-specific Natural Killer T-like cells against solid tumors and blood cancers

Acute supra-pharmacologic weight-based dexamethasone (AVM0703), 18 mgs/kg body weight, mobilizes endogenous bi-specific Natural Killer T-like cells independent of glucocorticoid receptor activation

On June 1, 2022 Asher Biotherapeutics, a biotechnology company developing precisely-targeted immunotherapies for cancer, autoimmune, and infectious diseases, reported that it has entered into a clinical trial collaboration and supply agreement with Merck (known as MSD outside of the United States and Canada) for a planned Phase 1a/1b dose escalation and expansion trial to evaluate AB248, Asher Bio’s novel investigational CD8-targeted interleukin 2 (IL-2), as a monotherapy and in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with locally advanced or metastatic solid tumors, including melanoma, renal cell carcinoma (RCC), non-small cell lung carcinoma (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN) (Press release, Asher Biotherapeutics, JUN 1, 2022, View Source [SID1234615378]). Under the terms of the agreement, Asher Bio is responsible for conducting the Phase 1a/1b trial, which it expects to initiate in the second half of 2022.

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Mechanistically, IL-2 signaling is complementary to PD-1 checkpoint blockade: checkpoint inhibitors release the brakes on T cells, allowing them to kill cancer cells, while IL-2 pushes on the gas pedal driving an increase in the number and activity of T cells. In the clinic, there have been studies conducted on high dose IL-2 as a monotherapy to treat PD-1 failures and on high dose IL-2 in combination with PD-1 checkpoint inhibitors in earlier lines of therapy that both demonstrated encouraging activity. However, despite high dose IL-2 efficacy in these settings, severe toxicities significantly hamper use of IL-2 in practice.

Asher Bio previously reported preclinical data from studies of a murine surrogate of AB248, which achieved significant anti-tumor activity as monotherapy and in combination with anti-PD1, without toxicity associated body weight loss. In comparison, treatment with a "not α" IL-2 achieved lower anti-tumor activity and was accompanied by body weight loss.

"We are looking forward to initiating this trial in collaboration with Merck to evaluate AB248 in combination with KEYTRUDA in a range of cancers," said Craig Gibbs, Ph.D., Chief Executive Officer of Asher Bio. "Treatment with PD-1 checkpoint blockade monotherapy or in combination with chemotherapy or another immunotherapy has become a recommended first line treatment in multiple indications. Yet for patients who failed to achieve a response or who relapse, treatment options are limited. In addition, there is a subset of first line patients where there is an opportunity to enhance the current standard of care. We believe that by precisely focusing the effect of IL-2 to the primary immune cell subset that drives anti-tumor efficacy, AB248 may have the potential to deliver a highly differentiated product profile that could become a backbone of immuno-oncology across a range of solid tumors."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.

About AB248
AB248 is a novel CD8+ T cell selective IL-2, generated by fusing a reduced potency IL-2 mutein to a humanized IgG1 anti-CD8β antibody. It was specifically engineered to selectively and potently expand CD8+ T-cells, while avoiding natural killer (NK) cells, which can act as a pharmacological sink and contribute to toxicity, and regulatory T (Treg) cells, which are immunosuppressive. In some preclinical studies, AB248 exhibits an approximately 1,000-fold preference for the activation of CD8+ T cells over NK cells and Tregs. In other nonclinical studies, AB248 has demonstrated potent anti-tumor activity both alone and in combination with PD-1 checkpoint blockade in a wide variety of murine tumor models.

On June 1, 2022 Arrakis Therapeutics, a biopharmaceutical company pioneering the discovery of a new class of small molecule medicines that directly target RNA, reported that Michael Gilman, Ph.D., Chief Executive Officer, will present a corporate overview at the Jefferies Healthcare Conference on Thursday, June 9, 2022 at 3:30 p.m. ET in New York (Press release, Arrakis Therapeutics, JUN 1, 2022, View Source [SID1234615377]).

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