On December 13, 2021 Bantam Pharmaceutical, a drug discovery and development company targeting selective modulation of mitochondrial dynamics in cancer, reported that data on the activity and mechanism of BTM-3566, a novel, first-in-class oral compound that targets mitochondrial dynamics leading to cellular stress and tumor cell apoptosis, was presented in an oral session at the 63rd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), virtually and in-person in Atlanta (Press release, Bantam Pharmaceutical, DEC 13, 2021, View Source [SID1234596988]). BTM-3566 is currently being developed for the treatment of hematological malignancies including Diffuse Large B-cell Lymphoma (DLBCL).

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The talk, entitled BTM-3566, a Novel Activator of the Mitochondrial Stress Response Promotes Robust Therapeutic Responses In Vitro and In Vivo in Diffuse Large B-Cell Lymphoma, was selected by ASH (Free ASH Whitepaper) as part of the session "Lymphoid Neoplasms: Targeting Mitochondrial Survival Pathways." Data presented showed BTM-3566 to be a highly potent activator of mitochondrial integrated stress response (ISR), which is well-tolerated in the pre-clinical setting with favorable pharmacokinetics. BTM-3566 induces rapid cell death in lymphoma cell lines, particularly those from DLBCL patients. In vivo, BTM-3566 was highly active in all patient-derived xenograft (PDX) models of DLBCL, and induced complete tumor regression in six out of eight models including those harboring genomic alterations usually associated with poor prognosis. Regressions were observed in multiple models of double-hit DLBCL.

"DLBCL that has relapsed or is refractory to standard therapy continues to be a challenge and treatments are especially limited for patients who are not candidates for stem cell transplantation or who have failed CAR-T cell therapy," said Adrian Schwarzer, M.D., Ph.D., the presenting author and Resident at the Department of Hematology, Oncology and Stem Cell Transplantation, Hannover Medical School in Hannover, Germany. "We are excited to see how BTM-3566 promoted complete tumor regression in vivo in mouse models with poor prognosis. We believe BTM-3566’s mechanism of action potentially defines a new class of compounds that activate, and regulate, the mitochondrial protease OMA1."

"We are encouraged by these strong results in pre-clinical studies, and pleased that ASH (Free ASH Whitepaper) selected this research for inclusion in its oral session on mitochondrial survival pathways," said Michael Stocum, President and Chief Executive Officer, Bantam Pharmaceuticals. "Importantly, these findings support our IND application in early 2022 and initiating first-in-human clinical trials in the first half of 2022."

View the abstract online at: View Source

Registered ASH (Free ASH Whitepaper) attendees can view the presentation online at: View Source

About BTM-3566

BTM-3566 is an orally-available novel small molecule compound with broad anti-cancer activity in hematologic and solid tumors, initially focused on Diffuse Large B-cell Lymphomas (DLBCL). BTM-3566’s anti-cancer mechanism of action is unique and differentiated from other therapeutics, disrupting mitochondrial function in tumor cells to induce apoptosis (cell death). An IND application for BTM-3566 in B-cell malignancies is being completed for submission in Q1 2022.

On December 13, 2021 Precigen, Inc., a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported that positive interim data at the 63rd ASH (Free ASH Whitepaper) Annual Meeting and Exposition (Abstract# 825) from the ongoing Phase 1/1b clinical study of PRGN-3006 UltraCAR-T in patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) and higher risk myelodysplastic syndromes (MDS) (clinical trial identifier: NCT03927261) (Press release, Precigen, DEC 13, 2021, View Source [SID1234596987]). The oral presentation was delivered by David Sallman, MD, Assistant Member in the Department of Malignant Hematology at the H. Lee Moffitt Cancer Center & Research Institute (Moffitt) and a lead investigator for the PRGN-3006 clinical trial.

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PRGN-3006 UltraCAR-T is a multigenic autologous CAR-T simultaneously expressing a CAR specifically targeting CD33; membrane bound IL-15 (mbIL15) for enhanced in vivo expansion and persistence; and a kill switch to conditionally eliminate CAR-T cells for an improved safety profile. CD33 is over-expressed on AML blasts with lesser expression on normal hematopoietic stem cells. PRGN-3006 UltraCAR-T has been granted Orphan Drug Designation in patients with AML by the US Food and Drug Administration (US FDA).

The Phase 1/1b clinical study is designed to enroll in two phases, an initial dose escalation phase followed by a dose expansion phase, to evaluate safety and determine the maximum tolerated dose of PRGN-3006 delivered via intravenous (IV) infusion without lymphodepletion (Cohort 1) or with lymphodepletion (Cohort 2). The study is also evaluating in vivo persistence and anti-tumor activity of PRGN-3006.

Today’s ASH (Free ASH Whitepaper) presentation included data from 15 r/r AML patients treated in the non-lymphodepletion cohort (N=9) and the lymphodepletion cohort (N=6). Patients were heavily pre-treated with a median of 4 (range: 1 to 6) and 3 (range: 1 to 7) prior regimens in the non-lymphodepletion and the lymphodepletion cohorts, respectively. Additionally, 33% and 50% of the patients had failed prior allogeneic hematopoietic stem cell transplant (allo-HSCT) in the non-lymphodepletion and the lymphodepletion cohorts, respectively. All patients received a single infusion of PRGN-3006.

Safety Data
PRGN-3006 was well-tolerated with no dose-limiting toxicities (DLTs) and no neurotoxicity at any dose level. Overall, there was low incidence of adverse events following PRGN-3006 infusion and the most common adverse events were decreased lymphocyte count, anemia and cytokine release syndrome (CRS). More than 70% of treatment emergent adverse events (TEAEs) were either Grade 1 or 2 with only one transient Grade 3 CRS reported (Dose Level 1, Cohort 1), which resolved in less than 24 hours with tocilizumab and dexamethasone. Other cases of CRS were Grade 1 or 2 and required either no intervention or resolved following standard CRS management. No subjects experienced a significant increase in serum IL-15, demonstrating that mbIL15 remains tethered to the UltraCAR-T cells as designed and is not released.

Clinical Activity
Non-lymphodepletion Cohort
Excellent dose-dependent expansion and persistence of PRGN-3006 in peripheral blood and bone marrow was observed following a single infusion, with detection of UltraCAR-T cells in blood for more than 7 months post-infusion highlighting the ability of UltraCAR-T cells to engraft and survive even in the absence of lymphodepletion. Peak expansion was observed between days 7 and 21 in the peripheral blood (FIGURE 1).

In the non-lymphodepletion cohort at the three dose levels evaluated, 3 out of 9 (33%) patients had Stable Disease (SD), per European LeukemiaNet (ELN) criteria, persisting for more than 3 months with one patient experiencing durable SD for more than 7 months with concomitant reduction in peripheral blast levels.

Lymphodepletion Cohort
Excellent dose-dependent expansion and persistence of PRGN-3006 in peripheral blood and bone marrow was observed following a single infusion, with detection of UltraCAR-T cells in blood for more than 3 months post-infusion. Peak expansion was observed between days 14 and 21 in the peripheral blood with higher peak expansion (> 10 fold) observed in the lymphodepletion cohort (FIGURE 2) at the same dose level.

An ORR of 50% (3 out of 6) was reported in the lymphodepletion cohort in patients treated at the two lowest dose levels. This included an ORR of 33% (1 out of 3) at Dose Level 1 and 67% (2 out of 3) at Dose Level 2 as summarized in TABLE 1. One responder (Dose Level 1) subsequently received allo-HSCT with ongoing survival greater than 1 year.

TABLE 1: Summary Objective Response Data for the Lymphodepletion Cohort

Dose Level
(DL)

AML Subtype

Dose Received

Age

Sex

Prior
Regimens*

Safety**

Objective Response***

DL 1

Persistent AML

8.7 x 106

60

F

2 prior:

CLAG and HiDAC

No incidence
of CRS,
neurotoxicity
or DLT

CRh at Day 84

DL 2

Extramedullary AML

28 x 106

53

M

7 prior: intensive chemo,
vidasia, venetoclax, FLAG,
anti-IDH1, allo-HSCT

No incidence
of CRS,
neurotoxicity
or DLT

PR#

AML

20 x 106

61

F

4 prior:

vyxeos, HMA+venetoclax,
allo-HSCT

CRS Grade 1,
with SAE skin
rash,
(possible
GVHD)

CRi at Day 28

CRh at Day 60

*CLAG=cladribine, cytarabine, and granulocyte-stimulating factor; HiDAC=high-dose cytarabine; FLAG=fludarabine, cytarabine and filgrastim; anti-IDH1=isocitrate dehydrogenases 1 inhibitor; HMA=hypomethylating agents (HMA); allo-HSCT= allogeneic hematopoietic stem cell transplant
**SAE=small ubiquitin-like modifier activating enzyme; GVHD=graft versus host disease
***Per ELN criteria; Complete Response with incomplete hematologic recovery (CRi); Complete response with hematologic recovery (CRh)
#Per RECIST v1.1; PR=partial response

Analysis of peripheral blood samples post PRGN-3006 infusion showed gene expression changes consistent with improvement in the immune compartment function for anti-tumor effect in responders. There was an increase in cytotoxicity, costimulatory signaling, and lymphoid compartment and decreased apoptosis pathway scores in the lymphodepletion cohort on Days 14 and 28 post PRGN-3006 treatment compared to baseline.

The study is anticipated to progress to the multicenter expansion phase with the plan to evaluate the potential of repeated dosing of PRGN-3006.

"The interim data for PRGN-3006 showed excellent, dose-dependent expansion and persistence of PRGN-3006 in peripheral blood and bone marrow following a single infusion, with detection of UltraCAR-T cells in blood more than 3 months post-infusion in the non-lymphodepletion and lymphodepletion cohorts," said David A. Sallman, MD, of Moffitt and lead investigator for the PRGN-3006 clinical study. "An ORR of 50% in patients treated at the two lowest dose levels in the lymphodepletion cohort is highly encouraging and the specifics of the responding patients suggest the potential for PRGN-3006 as a bridge to allo-HSCT, which is a very important potential treatment pathway for these patients."

"We are excited by these interim data, which clearly highlight the extraordinary potential and flexibility of the UltraCAR-T platform to deliver precision medicine to patients at any time, at any place and as many times as needed," said Helen Sabzevari, PhD, President and CEO of Precigen. "Based on the favorable safety profile and excellent expansion observed for both the lymphodepletion and the non-lymphodepletion cohorts, we believe UltraCAR-T cells have the potential to improve outcomes for cancer patients."

On December 13, 2021 IceCure Medical Ltd. (NASDAQ: ICCM) (TASE: ICCM) (the "Company" or "IceCure"), developer of minimally-invasive cryoablation technology, the ProSense System, that destroys tumors by freezing as an alternative to surgical tumor removal, reported the closing of its underwritten public offering of 3,892,152 shares of the Company’s ordinary shares, inclusive of 578,325 shares offered pursuant to the underwriters’ over-allotment option, at a price to the public of $3.45 per share, before underwriting discounts and commissions, and to certain investors in lieu of ordinary shares, pre-funded warrants to purchase up to an aggregate of 1,034,000 ordinary shares at a price to the public of $3.449 per pre-funded warrant, which represents the per share public offering price for the Ordinary Shares less the $0.001 per share exercise price for each such pre-funded warrant (Press release, IceCure Medical, DEC 13, 2021, View Source [SID1234596986]). The gross proceeds of the offering to the Company were approximately $17 million, before deducting underwriting discounts, commissions, and other offering expenses.

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A.G.P./Alliance Global Partners acted as sole book-running manager for the offering. Brookline Capital Markets, a division of Arcadia Securities, LLC, acted as a co-manager for the offering.

The Company intends to use the net proceeds from the offering for new product development, business development, working capital and general corporate purposes.

The offering was made by means of a prospectus. A copy of the final prospectus related to the offering may be obtained from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, or by email at [email protected] or by visiting EDGAR on the SEC’s website at www.sec.gov.

A registration statement relating to these securities was filed with the Securities and Exchange Commission and declared effective on December 8, 2021. This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 13, 2021 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, reported data from an ongoing pivotal Phase 2 study (CIBI376A201) evaluating parsaclisib, an potent, highly selective, next-generation oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), for the treatment of patients with relapsed or refractory follicular lymphoma in China (Press release, Innovent Biologics, DEC 13, 2021, View Source [SID1234596985]). These data were presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2021), held virtually from December 11–14, 2021.

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The CIBI376A201 study is a multi-center, single-arm, open-label pivotal Phase 2 study conducted in China evaluating parsaclisib as a treatment for patients with relapsed or refractory follicular lymphoma. The primary endpoint is objective response rate (ORR) as assessed by independent review committee (IRC); duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety and tolerability are among the secondary endpoints as assessed by investigators.

Eligible patients received parsaclisib 20 mg once daily for eight weeks followed by 2.5 mg once daily, till disease progression or intolerable adverse events. By the data cut-off date, 36 patients were enrolled, of which 24 were evaluable.

Key results of this study are: In 24 evaluable patients with r/r FL, ORR is 91.7% (95%CI : 73%, 99%), Complete Response(CR) is 16.7%, and Partial Response (PR) is 75%. As the results showed, parsaclisib was generally well tolerated with a manageable safety profile.

"We are glad that the data from study CIBI376A201 appears promising, which indicates the potential of parsaclisib to become a clinically valuable treatment for patients with relapsed or refractory follicular lymphoma," said Dr. Hui Zhou, Vice President of Innovent, "We hope the results of this study may potentially provide a new treatment option and help benefit those patients in China."

The leading PI of the study, Dr. Weili Zhao of Shanghai Jiaotong University Ruijin Hospital, stated "The interim analysis shows good response and a tolerable safety profile of parsaclisib in FL patients. We look forward to more exciting results to be revealed with the potential for parsaclisib to be a new effective treatment option for doctors to tackle relapsed or refractory follicular lymphoma."

Presentations are available on the ASH (Free ASH Whitepaper) website at: View Source

About Follicular Lymphoma

Follicular lymphoma is a B-cell cancer that originates from the uncontrolled division of specific types of B-cells known as centrocytes and centroblasts. Although it is classified as indolent lymphoma, and the current immunochemotherapy has achieved good efficacy, it still often relapses following by aggressive diseases, which may lead to death within 1 to 2 years. There is an unmet medical need for treatment options for recurrent/refractory follicular lymphoma.

About Parsaclisib

Parsaclisib is a potent, highly selective, next-generation investigational novel oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ). It is currently under evaluation as a monotherapy in several ongoing Phase 2 trials as a treatment for non-Hodgkin lymphomas (follicular, marginal zone and mantle cell); and autoimmune hemolytic anemia. Pivotal trials of parsaclisib in combination with ruxolitinib for the treatment of patients with myelofibrosis are underway; and there are plans to initiate a trial to evaluate parsaclisib in combination with tafasitamab for B-cell malignancies.

In December 2018, Innovent and Incyte entered into a strategic collaboration for three clinical-stage product candidates, including parsaclisib (PI3Kδ inhibitor). Under the terms of the agreement, Innovent has received the rights to develop and commercialize parsaclisib and two other assets in Mainland China, Hong Kong, Macau and Taiwan.

On December 13, 2021 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a precision oncology company targeting virus-associated malignancies, reported the presentation of new preclinical data on vecabrutinib, a reversible inhibitor of Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK), in oral and poster presentations at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Viracta Therapeutics, DEC 13, 2021, View Source [SID1234596984]).

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The oral presentation featured preclinical data indicating that vecabrutinib may enhance the efficacy and safety of CD19-targeted chimeric antigen receptor T (CART19) cell therapy. Though CART19 cell therapy has been shown to effectively treat certain hematological malignancies, rates of long-term durable response after therapy are low and the majority of patients develop resistance. Additionally, CAR T-cell therapies are associated with significant safety concerns such as cytokine release syndrome and neurotoxicity.

Key findings from the oral presentation include:

Vecabrutinib increased the cytotoxic activity of CART19 cells and maintained their proliferation capacity
Vecabrutinib enhanced CART19 cell anti-tumor activity in a murine mantle cell lymphoma model
Vecabrutinib reduced the level of pro-inflammatory cytokines known to cause toxicities associated with CAR T-cell therapy; these observations were consistent with data from a prior Phase 1 clinical trial evaluating vecabrutinib as a treatment for patients with B-cell malignancies
In a direct comparison with ibrutinib, only vecabrutinib continued to induce CAR-T cell proliferation at high doses
"These compelling preclinical findings demonstrate the potential of vecabrutinib to improve the efficacy of CAR T-cells while ameliorating many of the concerns that currently prevent their use outside of inpatient settings," said Ayman Elguindy, Ph.D., Chief Scientific Officer of Viracta. "If translated to the clinic, the positive effects of vecabrutinib could potentially expand the use and tolerability of CAR T-cell therapies and improve the outlook for patients with a variety of cancers."

In addition to the oral presentation, a poster presentation detailed preclinical findings of vecabrutinib in a murine model of sclerodermatous cGVHD, a complication occurring in patients following allogeneic stem cell transplantation. Data showed that vecabrutinib significantly reduced cGVHD symptoms including skin irritation, redness, alopecia, and diarrhea via modulation of pathogenetic B- and T-cell subsets.

Ivor Royston, M.D., President and Chief Executive Officer of Viracta, commented, "We believe vecabrutinib’s differentiated reversible kinase inhibitory profile and ability to modulate immune-related signaling pathways give it the potential to overcome the shortcomings of ibrutinib when combined with CAR T-cell therapy. Looking ahead, we are strategically evaluating clinical development options to assess the combination of vecabrutinib and CART19 cell therapy."

A copy of the ASH (Free ASH Whitepaper) presentations will be available by visiting the Events and Webcasts page of the Viracta website following the conference’s conclusion.

About Vecabrutinib

Vecabrutinib is a well-tolerated, selective, reversible, non-covalent inhibitor of Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK). Vecabrutinib is being studied as a potential enhancer of efficacy and safety of CAR T-cell therapy.