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Arbutus and Qilu Pharmaceutical Enter into an Exclusive Licensing Agreement and Strategic Partnership to Develop and Commercialize AB-729 in mainland China, Hong Kong, Macau and Taiwan

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.

HM43239 Demonstrates Durable Clinical Benefit in Acute Myeloid Leukemia

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.

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

Aprea Therapeutics Presents Primary Analysis from Phase 2 Trial of Eprenetapopt + Azacitidine for Post-Transplant Maintenance Therapy in TP53 Mutant MDS and AML at the 2021 American Society of Hematology (ASH) Annual Meeting

On December 13, 2021 Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate mutant tumor suppressor protein, p53, reported updated results from its Phase 2 trial evaluating eprenetapopt with azacitidine for post-transplant maintenance therapy in patients with TP53 mutant MDS and AML at the 2021 ASH (Free ASH Whitepaper) Annual Meeting (Press release, Aprea, DEC 13, 2021, View Source [SID1234596907]).

In 33 patients enrolled in the trial, the relapse free survival (RFS) at 1 year post-transplant was 60% and the median RFS was 12.5 months. The overall survival (OS) at 1 year post-transplant was 79%, with a median OS of 20.6 months. Published studies evaluating post-transplant outcomes in TP53 mutant MDS and AML patients have reported a 1-year post-transplant RFS of ~30% and a median OS of ~5-8 months. In addition, the post- transplant regimen of eprenetapopt and azacitidine was well tolerated among patients in the clinical trial. Given the encouraging data, the Company intends to explore opportunities to conduct future randomized clinical trials to further assess safety and efficacy of this combination in the post-transplant maintenance setting.

"This update of data at ASH (Free ASH Whitepaper), representing the primary analysis, highlights the very encouraging outcomes for these TP53 mutant MDS and AML patients who received eprenetapopt and azacitidine as post-transplant maintenance therapy," said trial principal investigator Asmita Mishra, M.D., of the H. Lee Moffitt Cancer Center and Research Institute. "As these patients characteristically have poor outcomes, even with transplantation, this post-transplant maintenance regimen is potentially paradigm-shifting and I look forward to investigating it further."

Slides for this presentation can be accessed from "Presentations" in the News and Events section of the Company’s website at Link.

Akoya Biosciences Announces a Groundbreaking Collaboration with PathAI to Combine Spatial Biology with AI-Powered Tools to Facilitate Discovery of Novel Predictive Biomarkers

On December 13, 2021 Akoya Biosciences, Inc., (Nasdaq: AKYA), The Spatial Biology Company, and PathAI, a global leader in artificial intelligence (AI)-powered technology for pathology, reported a collaboration to advance the discovery and validation of novel predictive biomarkers for immunotherapies (Press release, Akoya Biosciences, DEC 13, 2021, View Source [SID1234596906]). The partners will leverage their industry leading capabilities in spatial biology and deep data mining using Phenoptics, Akoya’s high throughput spatial phenotyping platform, and PathAI’s artificial intelligence tools and algorithms to enhance their shared biopharmaceutical partners’ ability to identify patients most likely to respond to drugs in clinical trials.

Akoya will work with PathAI to create a seamless interface between the Advanced Biopharma Solutions (ABS) service offerings and PathAI’s analytical capabilities to provide a powerful and complete solution for biopharma partners. This partnership and ABS’ recent CLIA certification represent significant milestones in advancing Akoya’s ability to serve the growing demand for spatial biomarkers in clinical trials.

"The combined power of spatial phenotyping and high throughput data sets from Akoya and PathAI’s algorithms can accelerate the discovery of spatial phenotypic signatures in the tumor microenvironment," said Dr. Andy Beck, CEO of PathAI. "This could streamline drug development to identify patients with a high likelihood of responding to immunotherapies."

Discovery and validation of novel biomarkers could have particularly important near-term implications for improving the efficacy rates of immuno-oncology treatments, an area of medicine that is revolutionizing cancer treatment. Spatial biology is a rapidly emerging scientific discipline that enables deeper understanding of cancer immunology by analyzing the spatial architecture of tumor tissue sections and mapping the complex organization and interactions of tumor and immune cells within the tumor microenvironment. These insights streamline drug development, clinical trials, and biomarker discovery, and are currently being applied to immunotherapy research.

"This collaboration takes Akoya’s ABS offering to the next level by providing biopharma partners with a comprehensive offering that integrates the most advanced technologies and know how in the field of spatial biomarkers and digital pathology," said Brian McKelligon, Chief Executive Officer of Akoya Biosciences. "The combination of our Phenoptics platform and PathAI’s AI-powered technology has the potential to transform biomarker use in clinical trials and ultimately impact cancer care."

Dr. Michael Montalto, Chief Scientific Officer of PathAI, will discuss the role of AI in spatial biomarker development at Akoya’s Spatial Day Event on December 15, 2021. Register at this link.

PharmaMar and Jazz Pharmaceuticals announce initiation of confirmatory phase III clinical trial of Zepzelca® (lurbinectedin) for the treatment of patients with relapsed Small Cell Lung Cancer

On December 13, 2021 PharmaMar (MSE:PHM) and partner Jazz Pharmaceuticals plc (Nasdaq:JAZZ) reported the initiation of a confirmatory Phase III clinical trial, LAGOON, evaluating Zepzelca (lurbinectedin) for the treatment of patients with relapsed Small Cell Lung Cancer (SCLC) (Press release, PharmaMar, DEC 13, 2021, View Source [SID1234596896]). The trial will measure Overall Survival (OS) as primary endpoint and Progression-Free Survival (PFS) as one of the secondary endpoints of lurbinectedin monotherapy or lurbinectedin in combination with irinotecan, compared with investigator’s choice of topotecan or irinotecan, in patients with SCLC whose disease has progressed following prior platinum-containing chemotherapy with or without anti-PD-1 or anti-PD-L1 agents.

"We are very excited about this trial, which is designed to reinforce lurbinectedin as a second-line treatment of choice in the U.S. and has the potential to bring our treatment to European patients,"

Said Ali Zeaiter, M.D., director of Clinical Development, PharmaMar Oncology Business Unit.

"There has been a strong clinical demand for lurbinectedin following the FDA’s accelerated approval, which demonstrates that this important therapy is filling a significant unmet need for the metastatic small cell lung cancer community,"

Said Rob Iannone, M.D., M.S.C.E., executive vice president, research and development and chief medical officer at Jazz Pharmaceuticals.

"We are committed to working with PharmaMar and the FDA to further demonstrate the clinical benefit of lurbinectedin and support conversion to full regulatory approval in the U.S."

LAGOON is a Phase III, randomized (1:1:1), multicenter, open-label clinical trial with three arms: one arm to receive lurbinectedin 3.2 mg/m2 as monotherapy (the approved dose in the U.S.), the second arm to receive lurbinectedin 2.0 mg/m2 in combination with irinotecan 75 mg/m2 and the third arm to receive topotecan or irinotecan based on the investigators’ choice. The trial will be conducted in patients with SCLC, whose disease has progressed following prior platinum-containing chemotherapy with or without anti-PD-1 or anti-PD-L1 agents. LAGOON is expected to enroll 705 patients from more than 100 sites mainly in North America and Europe.

The FDA approved lurbinectedin under accelerated approval in June 2020 for the treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy. The approval is based on Overall Response Rate (ORR) and Duration of Response (DoR) demonstrated in an open-label, monotherapy clinical study. If successful, LAGOON will serve as the confirmatory trial for lurbinectedin to secure full approval in the U.S. LAGOON will also be used as a registrational trial with the European Medicines Agency (EMA) to obtain marketing authorization in Europe. Jazz Pharmaceuticals holds the commercial rights for lurbinectedin in North America.

In 2021, lurbinectedin received marketing authorization in the United Arab Emirates, Canada, Australia and Singapore. Additional marketing authorizations are expected in 2022 and beyond.