On November 4, 2021 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company focused on creating and developing engineered IgM antibodies, reported its financial results for the third quarter ended September 30, 2021 and provided an update on recent developments (Press release, IGM Biosciences, NOV 4, 2021, View Source [SID1234594394]).

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"IGM continues to validate and expand the IgM platform through the clinical development of IGM-2323, our CD20 x CD3 T cell engager IgM antibody for the treatment of B cell proliferative diseases, IGM-8444, our Death Receptor 5 (DR5) agonist IgM antibody for the treatment of solid and hematologic cancers, and the establishment of our infectious diseases and autoimmunity and inflammation business units," said Fred Schwarzer, Chief Executive Officer of IGM Biosciences. "We plan to continue to expand our clinical development efforts, and by the end of 2022 we expect to be actively pursuing the clinical development of four oncology product candidates, led by two Phase 2 clinical studies of IGM-2323."

"We are encouraged by the emerging data from the clinical testing of IGM-2323 in our most fully explored titration dose cohort, 100 mg, where we have seen multiple complete responses in both diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), and we look forward to sharing the initial data from this 100 mg dose cohort at our American Society of Hematology (ASH) (Free ASH Whitepaper) presentation in December," said Chris Takimoto, M.D., Ph.D., F.A.C.P., Chief Medical Officer of IGM Biosciences. "While the number of patients we have treated at 100 mg is relatively small, we believe that the planned Phase 2 expansion studies could potentially provide the basis for accelerated review and approval. As a first step, consistent with the spirit of the U.S. Food and Drug Administration’s (FDA) Project Optimus, we plan to test doses of 100 mg and 300 mg in two separate randomized ‘pick the winner’ Phase 2 studies of 30 patients at each dose level, one in DLBCL and one in FL. We plan to then expand the Phase 2 studies at the optimal dose, while including the prior data from that dose for purposes of potential registration. While our safety profile at 600 mg and 1000 mg is consistent with lower doses and very encouraging, we do not plan to continue to explore doses higher than 300 mg for purposes of greater efficacy in either DLBCL or FL."

Pipeline Updates

IGM-2323 (CD20 x CD3)

Plans to initiate potentially registrational Phase 2 study. IGM reported plans to commence two potentially registrational Phase 2 studies to assess the safety and efficacy of two doses of IGM-2323, 100 mg and 300 mg, in patients with DLBCL and FL, one Phase 2 study in DLBCL and one Phase 2 study in FL. Each Phase 2 multicenter, open-label study will take place in two stages. In the first stage, cohorts of 30 patients at each dose level (100 mg and 300 mg) will be randomized in a ‘pick the winner’ design in both DLBCL and FL, respectively. The optimal dose arm in each Phase 2 clinical trial will then be expanded to additional patients in the second stage, potentially providing the basis for accelerated review and approval of IGM-2323, assuming the clinical data support that expansion.
Data from Phase 1 trial evaluating IGM-2323 selected for oral presentation at 2021 ASH (Free ASH Whitepaper) Annual Meeting and Exposition, being held virtually and in-person in Atlanta, Georgia, December 11-14, 2021. The results will be presented on Saturday, December 11, 2021, at 1:15 p.m. ET, in an oral presentation titled "A Phase 1 Dose Escalation Study of IGM-2323, a Novel Anti-CD20 x Anti-CD3 IgM T Cell Engager (TCE) in Patients with Advanced B-Cell Malignancies." In the ASH (Free ASH Whitepaper) oral presentation, IGM plans to present additional safety and efficacy data collected subsequent to the April 30, 2021 data cut-off for the ASH (Free ASH Whitepaper) abstract, which was released online today in Blood, ASH (Free ASH Whitepaper)’s official journal.
As described in the abstract released today, as of April 30, 2021, 29 patients had been enrolled in the Phase 1 study of IGM-2323: 12 at 5 fixed dose levels (0.5, 2.5, 10, 20, 100 mg) and 17 at 5 dose titration levels (100, 200, 300, 600, and 1000 mg). All 29 patients received at least one dose and were evaluable for safety. There were no dose limiting toxicities (DLTs) and no neurotoxicity adverse events (AEs). No patients discontinued due to an AE. Of the 29 patients evaluable for safety, 6 patients had cytokine release syndrome (CRS), primarily Grade 1. As previously described, there were only two higher grade CRS events as of April 30, 2021, one Grade 2 and one Grade 3. As previously described, the Grade 3 patient had been treated with an experimental CAR-T and had high baseline circulating B-cells. Of the 11 evaluable patients treated in the titration dose cohorts, as of the April 30, 2021 data cut-off, there were 5 responses, 3 complete responses and 2 partial responses.

IGM-8444 (DR5)

Clinical development of IGM-8444 advances. IGM continues to advance the clinical development of IGM-8444, the Company’s IgM DR5 agonist, in an open-label, multicenter, Phase I study of IGM-8444 as a single agent and in combination in subjects with relapsed and/or refractory solid and hematologic cancers.
Every two-week monotherapy dose escalation cohort successfully completed. IGM announced that it has successfully cleared its highest single-agent dose escalation cohort (10 mg/kg Q2W) with no DLTs and no clinically significant liver toxicity observed to date.
Second FOLFIRI dose cohort successfully completed. IGM also announced that it has cleared the second of four planned FOLFIRI combination dose escalation cohorts (1.0 mg/kg Q2W) with no DLTs and no clinically significant liver toxicity observed to date. IGM is currently enrolling patients in the third of four planned FOLFIRI combination dose escalation cohorts (3.0 mg/kg Q2W).
No acute or chronic clinically significant liver toxicity or clinically significant anti-drug antibodies observed to date. IGM also announced today that there have been no DLTs and no clinically significant liver toxicities observed to date in the 32 patients treated with IGM-8444, of whom 11 remain on treatment. Importantly, 7 patients have been on treatment for 5 or more months without showing signs of any chronic toxicities to date. No patient has discontinued treatment for drug related safety reasons, and no clinically significant anti-drug antibodies have been observed to date.
First patient dosed in combination with birinapant. IGM announced that it has treated its first patient in a combination clinical study of IGM-8444 with birinapant, a SMAC mimetic which binds to and degrades inhibitors of apoptosis proteins (IAPs) leading to apoptotic cell death in tumors. The combination of these two apoptotic agents, IGM-8444 and birinapant, has shown strong synergy in preclinical testing, and IGM has acquired exclusive worldwide rights to manufacture, develop and commercialize birinapant. The first patient in this combination cohort was successfully treated with no clinically significant adverse events observed to date. IGM is currently enrolling additional patients in this first birinapant dose cohort. IGM is also preparing to enroll patients with chronic lymphocytic leukemia/small lymphocytic lymphoma in a venetoclax-IGM-8444 combination cohort.
Markers of on-target biological activity observed. Signs of biological activity consistent with the activation of DR5 by a DR5 agonist have been observed in some patients, both in circulating biomarkers and histological tumor samples.
"IGM-8444’s toxicity profile to date, which has not shown any clinically significant liver toxicity, differentiates it from some of the second generation DR5 agonists that have struggled to progress in the clinic due to liver toxicity," said Dr. Takimoto. "Importantly, we believe this safety profile will be critical to successful combinations with other drugs, which we believe represent by far the most exciting and promising uses of DR5 agonists for the treatment of multiple solid and hematologic cancers. For this reason, our clinical development focus continues to be on combinations of IGM-8444 with standard of care and novel agents, such as FOLFIRI, venetoclax and birinapant."

IGM-6268 (COVID-19)

IGM-6268 for the treatment and prevention of COVID-19 expected to advance into the clinic in the fourth quarter. IGM-6268 is an IgM version of an anti-SARS-CoV-2 IgG monoclonal antibody and is being developed as an intranasally administered agent for the treatment and prevention of COVID-19. It is expected to start clinical development by the end of 2021, initially in healthy volunteers.
IGM-7354 (IL-15 x PD-L1)

Phase 1 clinical testing expected to initiate in 2022. IGM plans to initiate a Phase 1 study of IGM-7354, the Company’s IL‑15 x PD‑L1 bispecific IgM antibody, in solid tumors in 2022.
IGM-2644 (CD38 x CD3)

Phase 1 clinical testing expected to initiate in 2022. IGM announced today that it plans to initiate a Phase 1 study of IGM-2644, the Company’s CD38 x CD3 bispecific IgM antibody, in multiple myeloma in 2022.
"We believe the safety and efficacy profile that we have observed to date in the clinical development of IGM-2323, our T cell engaging IgM antibody targeting CD20 on lymphoma cells, is very encouraging with respect to the future clinical development of IGM-2644, our T cell engaging IgM antibody targeting CD38 on multiple myeloma cells, as it has shown similar preclinical safety and efficacy features to those we observed with IGM-2323," said Bruce Keyt, Ph.D., Chief Scientific Officer of IGM Biosciences. "We hope to file an investigational new drug (IND) application with the FDA and begin the Phase 1 clinical development of IGM-2644 next year."

Corporate Updates

Announced leadership appointments and formation of IGM Infectious Diseases and IGM Autoimmunity and Inflammation business units. The new business units will utilize and build upon IGM’s platform technology to create and develop novel IgM and IgA antibodies to address infectious diseases, autoimmunity and inflammation. To lead the IGM Autoimmunity and Inflammation business unit, IGM announced the appointment of Mary Beth Harler, M.D., as President. To lead the IGM Infectious Diseases business unit, IGM announced the appointments of John Shiver, Ph.D. and Tong-Ming Fu, M.D., Ph.D., as Chief Strategy Officer and Chief Scientific Officer, respectively.
Third Quarter 2021 Financial Results

Cash and Investments: Cash and investments as of September 30, 2021 were $265.6 million, compared to $366.3 million as of December 31, 2020.
Research and Development (R&D) Expenses: For the third quarter of 2021, R&D expenses were $34.2 million, compared to $15.8 million for the same period in 2020.
General and Administrative (G&A) Expenses: For the third quarter of 2021, G&A expenses were $10.0 million, compared to $4.7 million for the same period in 2020.
Net Loss: For the third quarter of 2021, net loss was $44.2 million, or a loss of $1.32 per share, compared to a net loss of $20.3 million, or a loss of $0.66 per share, for the same period in 2020.
2021 Financial Guidance

IGM reiterates its previously issued financial guidance expecting full year GAAP operating expenses to be between $175 million and $185 million including estimated non-cash stock-based compensation expense of approximately $25 million. IGM expects to end 2021 with a balance of over $200 million in cash and investments.

On November 4, 2021 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that, based on feedback from the U.S. Food and Drug Administration ("FDA") at a recent Type B meeting, where the Company provided the FDA with additional detailed data and the statistical analysis plan, the Company has requested a pre-BLA meeting for omburtamab for the treatment of pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma (Press release, Y-mAbs Therapeutics, NOV 4, 2021, View Source [SID1234594393]). The Company believes the pre-BLA meeting will be held in January 2022, and pending a positive meeting, the Company aims to initiate resubmission of the omburtamab BLA shortly thereafter.

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"We are very pleased to be aligned with the FDA on the next step towards the resubmission of the omburtamab BLA, and believe that, if approved, omburtamab will be of significant benefit to children with CNS/leptomeningeal metastasis from neuroblastoma, who are currently facing a significant unmet medical need," stated Thomas Gad, founder, Chairman and President.

Dr. Claus Moller, Chief Executive Officer, continued, "We are reconfirming our anticipated timeline for resubmission of the omburtamab BLA, as we believe we are still positioned to complete the submission during the course of the first quarter 2022, potentially allowing for FDA approval of omburtamab in the fourth quarter 2022."

Researchers at Memorial Sloan Kettering Cancer Center ("MSK") developed omburtamab, which is exclusively licensed by MSK to Y-mAbs. As a result of this licensing arrangement, MSK has institutional financial interests in the compound.

On November 4, 2021 X4 Pharmaceuticals, Inc. (Nasdaq: XFOR), a leader in the discovery and development of novel CXCR4-targeted small molecule therapeutics to benefit people with diseases of the immune system, reported financial results for the third quarter and nine months ended September 30, 2021 (Press release, X4 Pharmaceuticals, NOV 4, 2021, View Source [SID1234594391]). The company also provided a summary of the data contained within the seven abstracts submitted and accepted for presentation and/or publication at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place in Atlanta, Georgia and virtually December 11-14, 2021.

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"This has been an amazing quarter of progress for all of us at X4, as we completed enrollment in the Phase 3 trial of mavorixafor in its first indication of WHIM syndrome and are now looking ahead to sharing a broad array of clinical and scientific data in the fourth quarter that further support the potential of mavorixafor across multiple additional therapeutic areas," said Paula Ragan, Ph.D., President and Chief Executive Officer of X4. "As we continue to expand our pre-commercial activities for WHIM in anticipation of top-line data late next year, we are also working to build out our pipeline – further advancing clinical trials of mavorixafor in neutropenia and rare oncology indications, while also advancing our pre-clinical programs towards the clinic."

Key Takeaways from ASH (Free ASH Whitepaper) Abstracts Published Today

WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome:

Mavorixafor continues to show durable increases in neutrophils and lymphocytes, sustained improvements in infections and warts, and good tolerability in the ongoing Phase 2 open-label extension trial in WHIM syndrome.
Patient interviews revealed that study participants experienced good tolerability and beneficial treatment effects when dosed with mavorixafor.
Broader understanding of the clinical spectrum of WHIM syndrome and genotype/phenotype correlations have enabled assessment of novel CXCR4 variants for disease-correlation, including a newly discovered missense mutation (p.D84H) that is relatively frequent in the general population.
The D84H mutation is the first mutation identified outside of the C-terminus of the CXCR4 receptor showing gain-of-function signaling and disease phenotype; the frequency of the D84H mutation derived from broad population genomic databases robustly supports current estimates of U.S. WHIM prevalence of 1,000 to 3,500 or more.
This and other related research will be shared at the Investor Day on December 16.
Analyses of insurance claim databases using artificial intelligence indicate that the U.S. population of WHIM patients may be much larger than currently reported in the literature.
Results showed that there may be as many as 3,700 WHIM patients based on WHIM-like phenotypes described.
Data are consistent with novel genetic variant discoveries and genotype-phenotype correlations, building further confidence in estimates of potentially treatable WHIM patients in the U.S.
The company’s global Phase 3 clinical trial in WHIM syndrome (now fully enrolled) is the first double-blind, placebo-controlled, randomized trial in this patient population and the only one exploring an oral therapy. All enrolled patients had severe neutropenia and more than half are pediatric patients, illustrative of the severity and early onset of the disease. Top-line data from the trial are expected in the fourth quarter of 2022.
Chronic neutropenia and other indications:

Mavorixafor alone or in combination with other therapies is the first oral treatment to acutely and chronically increase total peripheral white blood cells (WBCs) 1.5- to 3-fold across all disease populations examined (WHIM syndrome, Waldenström’s macroglobulinemia, clear cell renal cell carcinoma, and healthy volunteers).
Further, mavorixafor’s ability to increase circulating WBCs (neutrophils, lymphocytes, and monocytes) across various disease states and in healthy individuals supports its potential utility in the treatment of patients with immunodeficiency, regardless of the presence or absence of CXCR4 mutations.
A Phase 1b trial in chronic neutropenia populations is ongoing to assess the potential of mavorixafor to treat broader neutropenias by increasing neutrophil counts, as well as other white blood cell types; initial data from this trial are expected to be presented in an ASH (Free ASH Whitepaper) poster presentation and at the Investor Day on December 16.
Waldenström’s macroglobulinemia (WM):

Additional preliminary clinical data are presented from the ongoing Phase 1b dose-escalation trial assessing the tolerability and efficacy, including clinical response rates, of mavorixafor in combination with ibrutinib in diagnosed WM patients with both MYD88 and CXCR4 mutations.
As of the abstract cutoff date of June 15, 2021, the overall response rate (minor response or better) for evaluable patients was 100% (N=8), with 4 of 8 patients achieving a major response (corresponding to >50% reduction in serum IgM) and 1 of 8 patients achieving very good partial response (corresponding to >90% reduction in serum IgM).
Additional clinical data are expected to be presented in an ASH (Free ASH Whitepaper) poster presentation and at the Investor Day on December 16.
Abstracts Accepted for Presentation and Publication at ASH (Free ASH Whitepaper)

Preliminary Clinical Response Data from a Phase 1b Study of Mavorixafor in Combination with Ibrutinib in Patients with Waldenström’s Macroglobulinemia with MYD88 and CXCR4 Mutations Poster Presentation on 12/11/2021 from 5:30 – 7:30 pm ET
Mavorixafor, an Oral CXCR4 Antagonist, for Treatment of Patients with WHIM Syndrome: Results from the Long-Term Extension of the Open-Label Phase 2 Study Poster Presentation on 12/11/2021 from 5:30 – 7:30 pm ET
Oral Administration of Mavorixafor, a CXCR4 Antagonist, Increases Peripheral White Blood Cell Counts across Different Disease States Poster Presentation on 12/12/2021 from 6:00 – 8:00 pm ET
Comprehensive in Vitro Characterization of CXCR4WHIM variants to Decipher Genotype–Phenotype Correlations in WHIM Syndrome Poster Presentation on 12/12/2021 from 6:00 – 8:00 pm ET
Characterization of a Novel Missense CXCR4 Mutation in a Patient With WHIM-like Syndrome Abstract Publication only
Application of an Artificial Intelligence/Machine Learning Model for Estimating Potential US Prevalence of WHIM Syndrome, a Rare Immunodeficiency, From Insurance Claims Data Abstract Publication only
Global Phase 3, Randomized, Placebo-Controlled Trial With Open-Label Extension Evaluating the Oral CXCR4 Antagonist Mavorixafor in Patients With WHIM Syndrome (4WHIM): Trial Design and Enrollment Abstract Publication only
Following the ASH (Free ASH Whitepaper) meeting, the company will be hosting an investor event on the morning of December 16. The call is expected to include commentary from prominent key opinion leaders (KOLs) as part of the program. Details will be forthcoming.

Third Quarter and Recent Highlights

X4 achieved a major milestone in early October, completing enrollment in the ongoing pivotal Phase 3 clinical trial (4WHIM) of mavorixafor in the treatment of patients with WHIM syndrome. Thirty-one adult and pediatric patients have been enrolled in the 4WHIM trial, which was originally designed to enroll 18-28 patients.
The company recently announced the appointment of Françoise de Craecker to the company’s Board of Directors and the recent hiring of Karolyn Park to the newly created role of Vice President, U.S. Commercial, significantly strengthening the company’s depth and breadth of commercial leadership experience in the strategic marketing of rare disease therapeutics.
The company announced the promotion of Mary DiBiase, Ph.D. to the newly created position of Chief Operating Officer, reflecting her long-standing contributions to the company and the advancement of mavorixafor into global late-stage clinical development.
Third Quarter 2021 Financial Results

Cash, Cash Equivalents & Restricted Cash: X4 had $77.7 million in cash, cash equivalents, and restricted cash as of September 30, 2021. The company continues to expect that its cash and cash equivalents will fund company operations into the fourth quarter of 2022.
Research and Development Expenses were $13.2 million for the third quarter ended September 30, 2021, as compared to $11.4 million for the comparable period in 2020. R&D expenses include $0.6 million and $1.0 million of certain non-cash expenses for the quarters ended September 30, 2021 and 2020, respectively.
General and Administrative Expenses were $5.9 million for the third quarter ended September 30, 2021, as compared to $5.6 million for the comparable period in 2020. G&A expenses include $0.9 million and $1.2 million of certain non-cash expenses for the quarters ended September 30, 2021 and 2020, respectively.
Net Loss: X4 reported a net loss of $20.2 million for the quarter ended September 30, 2021, as compared to a net loss of $17.4 million for the comparable period in 2020. Net losses include $1.5 million and $2.2 million of certain non-cash expenses for the quarters ended September 30, 2021 and 2020, respectively.
Conference Call and Webcast
X4 will host a conference call and webcast today at 9:05 a.m. ET to discuss the financial results and business highlights, as well as the abstracts accepted to this year’s ASH (Free ASH Whitepaper) Annual Meeting. The conference call can be accessed by dialing (866) 721-7655 from the United States or (409) 216-0009 internationally, followed by the conference ID: 7582968. The live webcast can be accessed on the investor relations section of X4 Pharmaceuticals’ website at www.x4pharma.com. Following the completion of the call, a webcast replay of the conference call will be available on the company website.

On November 4, 2021 Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions, announced today data from the ANCHOR Phase 1 study of KUR-502 to be highlighted in a poster presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held from December 11th to December 14th, 2021 (Press release, Athenex, NOV 4, 2021, View Source [SID1234594378]). The data demonstrates that allogeneic CD19 CAR-NKT cells are well-tolerated and can mediate objective responses in B-cell relapsed/refractory non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL) patients even at the low doses tested.

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"The early safety and clinical activity data are very encouraging," said Carlos Ramos, M.D., Professor at the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital and Houston Methodist Hospital and Principal Investigator. "The availability of a safe and effective off-the-shelf product would be a major advance in the care of these patients, and we are looking forward to treating additional patients at higher dose levels to further evaluate KUR-502."

Dan Lang, M.D., President, Athenex Cell Therapy, Vice President, Corporate Development and Communication commented, "We are excited about these early promising results from our first-in-human allogeneic study of CD19 CAR NKT cells in heavily pre-treated patients, including two patients who had previously failed autologous CAR-T therapies. We are encouraged that we have been able to demonstrate homing of allogeneic CAR-NKT cells to tumor, which is a differentiating feature of this platform. We look forward to accelerating clinical enrollment by bringing on additional clinical sites to the current study to generate more data, and further characterize the unique features and benefits of NKT cells over other cell therapy products based on T cells and NK cells."

Allogeneic NKT Cells Expressing a CD19-specific CAR in Patients with Relapsed or Refractory B-cell Malignancies: An Interim Analysis

The primary and secondary objectives of the phase I dose-escalation trial are to assess safety and anti-tumor activity of allogeneic NKT cells engineered to co-express a CD19-specific CAR, IL-15, and shRNAs targeting HLA class I and II molecules. Patients received a single infusion of 107 (DL 1) or 3×107 (DL 2) allogeneic CAR-NKT cells per square meter of body surface area following lymphodepleting conditioning with cyclophosphamide/fludarabine.

Four patients with relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL, cohort A) were enrolled on DL 1 (NHL-1, -2, -3) and DL 2 (NHL-4), and 1 patient with relapsed acute B-lymphoblastic leukemia (ALL, cohort B) was enrolled on DL 1 (ALL-1). Allogeneic CAR-NKT cells were manufactured from the leukapheresis product of one HLA-unmatched healthy individual and cryopreserved.

The most common adverse effects observed were nausea and grade 3-4 hematologic toxicities related to the lymphodepletion chemotherapy. There were no early adverse events attributable to the cellular product except grade 1 cytokine release syndrome in one patient.

Of the 4 NHL patients, 2 had a partial response (NHL-1, -and -4) and 1 had a CR (NHL-2). The ALL patient achieved a CRi and showed no evidence of leukemia by morphology, flow cytometry, or next-generation sequencing at 4 weeks.

In vivo expansion of donor-derived NKT and CAR-NKT cells was detected in the peripheral blood of NHL-4 and ALL-1 that peaked at 1 week post-infusion in both cases as determined by flow cytometry and qPCR. While CAR-NKT cells were not detected in the peripheral blood of the first three NHL patients beyond three hours post-infusion, they were found in tumor tissues collected from the two biopsied NHL patients at up to 5 weeks post infusion. In patient NHL-2, a 2000-fold expansion of recipient NKTs with a skewed T cell receptor repertoire was also observed; this population peaked at 6 weeks post-treatment and remain elevated through 12 weeks.

About the Phase I Study of KUR-502 (Allogeneic CD19 CAR-NKT Cells) in Patients with Relapsed or Refractory B-Cell Malignancies (ANCHOR)

The phase I study is an open-label, dose-escalation study. NKT cells were isolated from the leukapheresis product of one HLA-unmatched healthy individual, transduced with the CAR, expanded ex vivo for 14 days (99.8% NKT purity), and cryopreserved. Patients received 107 (DL 1) or 3×107 (DL 2) CAR-NKT cells per square meter of body surface area following lymphodepleting conditioning with cyclophosphamide/fludarabine. Adverse events were evaluated per NCI criteria. When accessible, patients underwent core biopsies of an involved site at 2-5 weeks post-infusion. Response to therapy was assessed at 4 weeks per Lugano Criteria (for NHL) or NCCN guidelines (for ALL).

For further information about the study, visit ClinicalTrials.gov, identifier: NCT03774654.

On November 4, 2021 Geron Corporation (Nasdaq: GERN), a late-stage biopharmaceutical company focused on the development and commercialization of treatments for hematologic malignancies, reported that three abstracts related to imetelstat, the Company’s first-in-class telomerase inhibitor, have been accepted as poster presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to be held from December 11-14, 2021 (Press release, Geron, NOV 4, 2021, View Source [SID1234594377]). The abstracts are available on the ASH (Free ASH Whitepaper) website at www.hematology.org.

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"The abstracts for this year’s ASH (Free ASH Whitepaper) Meeting reflect the breadth of ongoing activity with imetelstat from pre-clinical studies in a new indication, as well as use of imetelstat as a single agent and in combination with other therapies, to analyses of clinical data supporting our Phase 3 development," said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. "We look forward to continued work in these areas as we expand the potential applications for imetelstat in hematologic malignancies."

Clinical Data – Lower Risk Myelodysplastic Syndromes (MDS)

Abstract Title: On-Target Activity of Imetelstat Correlates with Clinical Benefits, Including Overall Survival (OS), in Heavily Transfused Non-Del(5q) Lower Risk MDS (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs)

The abstract describes new analyses of data from the IMerge Phase 2 clinical trial. In the analyses, a significant correlation was observed between achieving an optimal pharmacodynamic (PD) effect in imetelstat-treated patients with durable red blood cell transfusion independence (RBC-TI). In addition, a trend of improved overall survival rate was seen in patients who achieved optimal PD effect. The authors believe these results demonstrate a potential link between imetelstat activity and clinical efficacy. Additionally, patients in IMerge Phase 2 who achieved an optimal PD effect with imetelstat treatment did not have higher rates of cytopenias or liver enzyme elevations compared to patients without an optimal PD effect.

Poster Presentation Details
Abstract: #2598
Date: Sunday, December 12, 2021
Time: 6:00 p.m. – 8:00 p.m. ET

Pre-Clinical Data – Pediatric Acute Myeloid Leukemia

Abstract Title: Imetelstat Significantly Reduces Leukemia Stem Cells in Patient-Derived Xenograft Models of Pediatric AML

The abstract reports results from pre-clinical studies of imetelstat in pediatric acute myeloid leukemia (AML) cell lines (in vitro studies) and patient derived (PDX) mouse models (in vivo studies). The efficacy of imetelstat either as a single agent or in combination with chemotherapy or azacitidine was evaluated. In cell line experiments, imetelstat treatment resulted in cell apoptosis/death of leukemia stem cells (LSCs) in a dose-dependent manner. In the in vivo studies, imetelstat treatment reduced LSC numbers and increased median survival in mice. In addition, combining imetelstat with chemotherapy or azacitidine further enhanced activity against LSCs. The authors conclude that the results of these pre-clinical studies suggest imetelstat could represent an effective therapeutic strategy for pediatric AML.

Poster Presentation Details
Abstract: #3352
Date: Monday, December 13, 2021
Time: 6:00 p.m. – 8:00 p.m. ET

Trials in Progress Poster Presentation – IMpactMF Phase 3 trial in Refractory MF

Abstracts for this category describe innovative clinical trials that have not reached their primary endpoint to provide opportunities for early engagement and collaboration amongst investigators, translational research, clinical and industry investigators, statisticians and regulators.

Abstract Title:A Randomized Open-Label, Phase 3 Study to Evaluate Imetelstat Versus Best Available Therapy (BAT) in Patients with Intermediate-2 (Int-2) or High-risk Myelofibrosis (MF) Refractory to Janus Kinase Inhibitor (JAKi)

Poster Presentation Details
Abstract: #1503
Date: Saturday, December 11, 2021
Time: 6:00 p.m. – 8:00 p.m. ET

In accordance with ASH (Free ASH Whitepaper) policies, abstracts submitted to the ASH (Free ASH Whitepaper) Annual Meeting are embargoed from the time of submission. To be eligible for presentation at the ASH (Free ASH Whitepaper) Annual Meeting, any additional data or information to be presented at the Annual Meeting may not be made public before the presentation. The posters will be available at www.geron.com/r-d/publications following the ASH (Free ASH Whitepaper) Annual Meeting presentations.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in myeloid hematologic malignancies. Data from Phase 2 clinical trials provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis-stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment.