On December 13, 2021 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported a poster highlighting the safety and preliminary efficacy data of its Phase 2 study of prexigebersen (BP1001) was presented at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place from December 11-14, 2021 (Press release, Bio-Path Holdings, DEC 13, 2021, View Source [SID1234596912]).

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The poster, titled, "Safety and Efficacy of Lower Intensity Induction Therapy with Intravenous Prexigebersen (BP1001) in Patients with High-Risk and Relapsed/Refractory Acute Myeloid Leukemia (AML)," was presented by Maro Ohanian, D.O., Department of Leukemia, University of Texas MD Anderson Cancer Center. The poster described the safety and preliminary efficacy of Bio-Path’s lead drug candidate, prexigebersen (liposomal Grb2 antisense), from a Phase 2 study in combination with decitabine or decitabine plus venetoclax as a potential treatment for patients diagnosed with AML.

"Our study’s novel clinical trial protocol was designed to adjust for the inclusion of newly approved therapies that we believed would be enhanced from combination with our DNAbilize technology," said Peter Nielsen, President and Chief Executive Officer of Bio-Path Holdings. "This robust design provided for early evaluation of various combinations of prexigebersen to optimize the best potential outcomes for patients and allows for the most expeditious pathway to market. We are delighted to have these safety and preliminary efficacy data presented among an audience dedicated to bringing new cancer treatments to patients."

The Phase 2 clinical trial is a multi-center, open label study with three patient cohorts:

•Untreated AML patients treated with prexigebersen in combination with decitabine plus venetoclax;
•Refractory/relapsed AML patients treated with prexigebersen in combination with decitabine plus venetoclax; and
•Refractory/relapsed AML patients, resistant or intolerant to venetoclax, treated with prexigebersen in combination with decitabine.

The primary objective of the study is to assess whether prexigebersen in combination with decitabine plus venetoclax provides higher response rates than decitabine plus venetoclax in AML patients and whether prexigebersen in combination with decitabine provides higher response rates than decitabine alone in AML patients. The study was amended to obtain safety run-in data for patients treated with prexigebersen + decitabine first before proceeding to safety run-in for patients treated with prexigebersen + decitabine + venetoclax. In the Poster we report the safety run-in and efficacy data of AML patients treated with prexigebersen + decitabine or prexigebersen + decitabine + venetoclax.

Data Highlights

Six patients, including four patients (67%) with de novo AML and two secondary AML patients (33%), were treated with at least one cycle of prexigebersen + decitabine combination therapy. All patients in this cohort (median age 72 years) were considered high risk due to having either adverse risk status by ELN (n=5) or treated secondary AML (n=1). Data showed that adverse events (AEs) were generally consistent with those expected with decitabine and/or AML. Three of the six patients (50%) had a response, including two de novo patients (33%) who achieved a CRi (complete remission with incomplete blood count recovery) and one secondary AML patient (17%) who achieved a partial remission (PR). Patients with these conditions generally have a less than 20% CR/CRi response rate.

Six patients were treated with at least one cycle of prexigebersen + decitabine + venetoclax combination therapy. Of the six patients, two (33%) had de novo AML and four (67%) were relapsed/refractory. All patients in this cohort were adverse-risk by ELN (n=2) or relapsed/refractory (n=4). AEs were generally consistent with decitabine and venetoclax treatment and/or for AML. Four patients (67%) achieved a complete remission (CR)/CRi/morphological leukemia free state (MLFS) (n=1/2/1) and one (17%) achieved a PR. Of these five patients, three were relapsed/refractory (75% of relapsed/refractory patients) (1 CR/1 CRi/1 MLFS) and two were de novo (1 CRi/1 PR) (100% of the de novo patients). CR rates to combination treatment with decitabine and venetoclax for relapsed/refractory AML patients are 42-52%1,2 and 0-39%1,2 for relapsed/refractory secondary AML patients.

The preliminary efficacy data are compelling and show that prexigebersen -based combination therapy was not only safely administered to high-risk and relapsed/refractory AML patients considered unsuitable for standard chemotherapy, but also

demonstrated encouraging efficacy signals. This is particularly encouraging as relapsed/refractory patients are a challenging population in which current treatment options are suboptimal.

About Prexigebersen (BP1001)

Prexigebersen is a neutral liposome incorporated with nuclease-resistant, hydrophobic P-ethoxy antisense oligodeoxynucleotides targeted to Grb2 mRNA. Grb2 is an adaptor protein that links oncogenic tyrosine kinases with downstream kinases, such as ERK and AKT, which are critical to cell proliferation and survival.

On December 13, 2021 BerGenBio ASA (OSE:BGBIO), BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, reported that it is presenting updated data from the Company’s Phase II study of bemcentinib (BCBC003) in a poster presentation today at the 63rd Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting (Press release, BerGenBio, DEC 13, 2021, View Source [SID1234596911]).

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Professor Sonja Loges will provide an update from the Company’s Phase II study (BGBC003) of bemcentinib in combination with low dose cytarabine (LDAC) in older, relapsed and refractory AML patients unfit for intensive chemotherapy.

The data presented indicate that bemcentinib in combination with LDAC is well tolerated and offers meaningful clinical benefits. Translational research has identified immune-based activity associated with response to treatment, demonstrating that bemcentinib elicits activation of CD8+ T cells and B cells/plasma cells, two major adaptive immune cell populations responsible for anti-AML immune responses. Survival data measured as median Overall Survival (mOS) in older unfit relapsed AML patients looks encouraging compared to historical controls all through not yet matured.

Professor Sonja Loges, Chief Investigator of the BGBC003 trial commented: "The data on relapsed AML patients who currently have very few treatment options, is very encouraging. These results affirm our belief that the combination of bemcentinib and LDAC provides meaningful clinical benefits."

Details of the presentation:

Title: Bemcentinib (Oral AXL Inhibitor) in combination with Low-dose Cytarabine Is Well Tolerated and Efficacious in Older Relapsed AML Patients. Updates from the Ongoing Phase II Trial (NCT02488408) and Preliminary Translational Results indicating Bemcentinib elicits anti-AML immune responses.

Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III

Time, Location: 6.00 – 8.00 PM Eastern, Georgia World Congress Center, Hall B5

On December 13, 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, reported it will host a virtual Key Opinion Leader (KOL) event today at 9:00am ET to discuss its NKT cell therapy programs (Press release, Athenex, DEC 13, 2021, View Source [SID1234596910]).

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Athenex had previously announced best responses from five patients of 2 partial responses (PR), 1 complete response with incomplete hematological recovery (CRi) and 1 complete response (CR) from the ANCHOR Phase 1 study of KUR-502 (allogeneic CD19 CAR-NKT cells) in relapsed /refractory lymphoma and leukemia. At the ASH (Free ASH Whitepaper) Annual Meeting yesterday, the Company provided updated results from the study, which included a conversion of one patient (NHL-4) treated with dose level (DL) 2, from a PR to a CR. Safety profile of treatment with the allogeneic CAR-NKT cells remains favorable and further enrollment is ongoing.

Register for the KOL webinar on the Investor Relations portion of the website.

The webinar will feature presentations by KOLs Leonid Metelitsa, M.D., and Carlos Ramos, M.D., both from Baylor College of Medicine, and Sattva Neelapu, M.D., from MD Anderson Cancer Center. Dr. Metelitsa will provide an overview of Athenex’s CAR-NKT cell-based approaches. Dr. Ramos will discuss the interim data from the ongoing ANCHOR study evaluating KUR-502 in relapsed or refractory lymphoma and leukemia. Dr. Neelapu will discuss the current treatment landscape and unmet medical needs in lymphoma and leukemia.

Presentations from Kurt Gunter, M.D., Chief Medical Officer for Cell Therapy at Athenex, and Daniel Lang, M.D., President of Athenex Cell Therapy, will follow to discuss clinical milestones and company objectives.

A question-and-answer session will follow the formal presentations.

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 December 13, 2021 Arbutus Biopharma Corporation (Nasdaq: ABUS), a clinical-stage biopharmaceutical company dedicated to developing a cure for people with chronic hepatitis B virus (HBV) infection, and Qilu Pharmaceutical, one of the leading pharmaceutical companies in China, reported that the companies have entered into an exclusive licensing agreement and strategic partnership for the development and commercialization of AB-729 for the treatment or prevention of hepatitis B in mainland China, Hong Kong, Macau and Taiwan (Press release, Arbutus Biopharma, DEC 13, 2021, View Source [SID1234596909]).

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AB-729 is Arbutus’s lead RNA interference (RNAi) therapeutic that is currently in multiple Phase 2a proof-of-concept clinical trials designed to evaluate it in combination with other approved or investigational agents.

William Collier, President and Chief Executive Officer of Arbutus Biopharma, commented, "Qilu is an ideal partner for our AB-729 RNAi therapeutic given their extensive development, regulatory and commercialization capabilities in China. We are now positioned to bring AB-729 to the largest HBV patient population in need of a cure and to tap into one of the largest and most promising healthcare markets worldwide. We are committed to working with Qilu in this partnership which further validates the potential of AB-729 to address the unmet medical need in HBV."

Qilu Pharmaceutical Chief Executive Officer, Ms. Yan Li commented, "The HBV patient population is significant in China. Based on clinical data achieved to-date, we believe in the potential of AB-729 to be a safe and effective treatment option in treating HBV. We look forward to collaborating with Arbutus to maximize the potential clinical value that AB-729 can bring to and benefit the millions of underserved HBV patients in China."

Under the terms of the agreement, Arbutus will receive a $40 million upfront payment and will be entitled to additional payments of up to $245 million upon reaching certain development, regulatory and sales milestones. The above amounts are net of withholding taxes. Qilu will be responsible for funding all development and commercialization activities for mainland China, Hong Kong, Macau and Taiwan. Arbutus is also entitled to receive double-digit tiered royalties up to the low twenties percent on annual net sales. In addition, Qilu will make a $15 million equity investment in Arbutus common shares at a price of $4.19 per share, a 15% premium of Arbutus’ previous 30-day average closing stock price calculated from December 10, 2021.

The common shares to be sold in the private placement have been offered only to certain institutional and/or accredited investors in reliance upon an exemption from the registration requirements of the Securities Act of 1933, as amended (the "Securities Act"). The common shares have not been registered under the Securities Act or any state or other securities laws and may not be offered or sold in the United States absent registration or an applicable exemption from registration requirements of the Securities Act and applicable state securities laws. The Securities and Exchange Commission has not passed upon the merits of or given its approval to the common shares, the terms of the private placement or the accuracy or completeness of any private placement materials. The common shares sold in the private placement are subject to legal restrictions on transfer.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification or otherwise under the securities laws of any such state or jurisdiction.

About AB-729

AB-729 is an RNA interference (RNAi) therapeutic specifically designed to reduce all HBV viral proteins and antigens, including hepatitis B surface antigen, which is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus. AB-729 targets hepatocytes using Arbutus’ novel covalently conjugated N-acetylgalactosamine (GalNAc) delivery technology that enables subcutaneous delivery. Clinical data generated thus far has shown single- and multi-doses of AB-729 to be generally safe and well-tolerated while providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA.

About HBV

Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV can cause chronic infection which leads to a higher risk of death from cirrhosis and liver cancer. Chronic HBV infection represents a significant unmet medical need. The World Health Organization estimates that over 250 million people worldwide suffer from chronic HBV infection, while other estimates indicate that approximately 2 million people in the United States suffer from chronic HBV infection. Approximately 900,000 people die every year from complications related to chronic HBV infection despite the availability of effective vaccines and current treatment options.

On December 13, 2021 Aptose Biosciences Inc. ("Aptose") (NASDAQ: APTO, TSX: APS) reported that the oral myeloid kinome inhibitor HM43239 has demonstrated durable single agent activity in patients with relapsed or refractory acute myeloid leukemia (AML) (Press release, Aptose Biosciences, DEC 13, 2021, View Source [SID1234596908]). Data were presented in an oral presentation today at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual meeting by lead investigator Naval G. Daver, M.D., Associate Professor in the Department of Leukemia at MD Anderson Cancer Center.

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HM43239 is an oral, once-daily, highly potent myeloid kinome inhibitor (MKI) designed to target key kinases operative in myeloid malignancies. In earlier preclinical studies, HM43239 demonstrated potent in vitro and in vivo activity against FLT3 ITD mutated as well as resistance-conferring D835 and gatekeeper (F691) TKD mutated AML. Additionally, HM43239 inhibited phosphorylation of SYK, known to be highly activated in AML and associated with resistance to FLT3 targeted therapy.

In the ongoing international Phase 1/2 study, thirty-four relapsed/refractory patients who had received at least one prior line of therapy were enrolled at multiple centers between March 2019 and August 2021, and treated at doses escalating from 20 mg to 160 mg. HM43239 delivered multiple complete responses (CR) and demonstrated clinically meaningful benefit in all responders, by either bridging successfully to hematopoietic stem cell transplant (HSCT) or leading to a durable response, as well as a favorable safety profile across all treated patients.

Highlights of Dr. Daver’s ASH (Free ASH Whitepaper) oral presentation:

Among FLT3 mutant patients treated with 80 mg, 3 of 8 (37.5%) achieved a durable composite complete response (CRc, CR + CRi).
At the 80 mg dose, a composite CRc rate of 25% was observed in both FLT3 mutant (including a prior gilteritinib failure patient) and FLT3 wild-type AML (including >1 year duration of response in a relapsed TP53m AML patient unfit for HSCT).
At the 80 mg dose, 4 of 5 (80%) responders advanced to HSCT.
Recently, another prior gilteritinib failure patient achieved PR after one cycle at the 120 mg dose.
HM43239 showed a favorable safety profile with only mild AEs and no DLTs up to 160 mg per day, and no drug discontinuations from drug related toxicity.
HM43239 plasma inhibitory assay (PIA) activity was dose-dependent with up to 90% phospho-FLT3 inhibition at dose levels ≥ 80 mg.
The study is ongoing across several cohorts – the dose escalation cohort of 200 mg and the dose expansion cohorts of 120 mg and 160 mg are currently enrolling.
"HM43239 demonstrated clear genotype-agnostic clinical activity as a single-agent in one of the most challenging and most heterogeneus disease settings in oncology today – relapsed and refractory AML," said Rafael Bejar, M.D., Ph.D., Chief Medical Officer. "Importantly, HM43239 has demonstrated activity in patients with FLT3 wild-type AML, FLT3 mutated AML, NPM1 mutated AML, as well as in patients with mutations historically associated with resistance to targeted therapy, such as TP53, NRAS, KRAS, and others. We believe that the clinical activity observed to date could support a broad expansion program covering multiple genotypes and disease stages in AML, both as monotherapy and in combination with other active agents."

In addition, clinical data for luxeptinib and APTO-253 were presented at ASH (Free ASH Whitepaper). The posters are now available on the presentations page of the Aptose website here.

Clinical data from luxeptinib in patients with relapsed or refractory B-cell malignancies and relapsed or refractory AML were presented in poster presentations on Saturday by lead investigators Felipe Samaniego, M.D., Professor in the Department of Lymphoma and Myeloma at MD Anderson Cancer Center, and Aaron Goldberg, M.D., Ph.D, from the Department of Medicine, Leukemia Service, Memorial Sloan-Kettering Cancer Center. In both of these Phase 1/2 studies, luxeptinib has been generally well tolerated at dose levels of 450, 600 and 750 mg BID over multiple cycles, and is currently being dosed in 900 mg BID cohorts in parallel. Target engagement of BTK and FLT3, and anti-tumor activity, including dose- and exposure-dependent tumor reductions, have been observed in multiple patients collectively between the studies, including in patients with FL, DLBCL, CLL/SLL, and AML. In parallel with the ongoing dose escalation of the current formulation of luxeptinib in patients with B-cell malignancies and AML, Aptose has made significant progress in the development of a "next generation" formulation that could reduce total API administered, reduce pill burden, improve absorption, and increase exposure. Aptose expects to begin testing this new formulation of luxeptinib in the ongoing studies in patients with hematologic malignancies in the first half of 2022.

Clinical data from APTO-253 were presented in a poster presentation on Monday at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual meeting by lead investigator Maro Ohanian, D.O., Associate Professor in the Department of Leukemia at MD Anderson Cancer Center. In an ongoing Phase 1a/b trial, APTO-253 has been well-tolerated in the patients treated at 20, 40, 66, 100, 150 and 210 mg/m2 over multiple cycles, supporting continued dose escalation. In parallel with the ongoing dose escalation of APTO-253, Aptose has started to explore strategic alternatives to support the further development of APTO-253 in hematologic malignancies and solid tumors.

"Drug resistance remains a tremendous challenge in hematologic malignancies, and we plan to leverage our growing bench of kinase inhibitors to tackle unmet needs across multiple indications and multiple disease genotypes. Our newest and most mature investigational drug, HM43239, is demonstrating activity against some of the most challenging AML genotypes and we look forward to continuing to advance it towards registration-enabling studies," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "Luxeptinib also continues to show positive trends of activity in both B-cell cancers and AML. We look forward to bringing on a new formulation of Lux that may help increase exposure levels further, and potentially deliver faster and deeper anti-tumor activity in hematologic malignancies."

Aptose will be holding a corporate update to discuss these data and updates today, December 13, at 5:30 PM ET:

Aptose Corporate Update Details

Date & Time: Monday, December 13, 2021, 5:30 PM ET

Participant Webcast Link: Link