PCNA

Planned Phase 2b trial expected to enroll 200 participants at U.S. sites Study design and protocol informed by recent positive discussions with U.S. Food and Drug Administration Prior dose-ranging Phase 2b trial demonstrated durable treatment effects with ATX101 versus standard-of-care bupivacaine based on pain intensity out to four weeks, with less use of opioids for pain relief while achieving faster improvement in function SAN JOSE, Calif.--(BUSINESS WIRE)-- Allay Therapeutics, a clinical-stage biotechnology company pioneering ultra-sustained analgesic products to transform post-surgical pain management and recuperation, today announced plans to proceed to a Phase 2b registration trial of its lead investigational product ATX101. The clinical trial builds on a strong foundation of clinical data from prior exploratory dose-ranging studies and is informed by recent discussions with the U.S. Food and Drug Administration (FDA) on the study design and protocol. If successful, this Phase 2b registration trial would support a new drug application (NDA) filed with the FDA. “We’re excited to reach this important milestone following a productive dialogue with the FDA to establish a clear path forward to evaluating ATX101 and further demonstrating its potential as a post-surgical pain management therapeutic,” said Adam Gridley, Chief Executive Officer at Allay Therapeutics. “The encouraging data from our recently completed Phase 2b dose-ranging trial provide compelling support for our registration clinical trial design, and we look forward to working closely with investigators to fully assess ATX101’s impact on patient recovery and recuperation following total knee replacement.” The Phase 2b registration trial of 200 participants undergoing total knee arthroplasty (replacement, or TKA surgery) will be conducted at multiple U.S. sites and is a three-arm randomized controlled study evaluating treatment with ATX101 1,500 mg versus placebo or a bupivacaine active comparator. The primary endpoint will be the area under the curve (AUC) of pain intensity as measured by the NRS-Rest over several weeks, with secondary endpoints evaluating reduction in use of opioids, opioid-related side effects, and improvement in physical function. The trial will assess and inform additional functional and health economics endpoints for an anticipated global Phase 3 registration study that would support an NDA filing. Allay’s recently completed dose-ranging Phase 2b trial enrolled 112 participants before being concluded early based on a positive interim analysis. Data showed that ATX101 achieved sustained, clinically meaningful post-surgical pain relief for up to four weeks following TKA compared to the standard of care (SOC) active comparator, bupivacaine. Treatment with ATX101 resulted in a decrease in opioid use as well as a decrease in opioid-related side effects and meaningful improvements in functional activities up to 60 days following surgery. About ATX101 ATX101 is a novel investigational configuration of an approved, well-characterized, validated intracellular sodium ion channel blocker, bupivacaine, and a biopolymer that has been designed to provide weeks of pain relief following total knee arthroplasty (TKA, or replacement), a common orthopedic surgery. ATX101 has a high density of drug within its small footprint to allow for ultra-sustained analgesia. It is placed in minutes at the end of standard surgery to deliver its analgesic effect over weeks before eventually dissolving into water and carbon dioxide. The simple procedure does not require specialized training and is intended to replace the existing complex mix of analgesic products used for shorter-term pain management in the post-surgical setting. ATX101 is an investigational product that has not been approved by the U.S. Food and Drug Administration. About Allay Therapeutics Allay Therapeutics is pioneering ultra-sustained analgesic products to transform post-surgical pain management and recuperation for patients and physicians. Our proprietary technology platform combines validated non-opioid analgesics and biopolymers to create dissolvable candidates to deliver pain relief within a targeted site over weeks: an order of magnitude greater than the longest-lasting pain treatments currently available. Our platform and vision were shaped by The Foundry incubator and Lightstone Venture’s Singapore Fund. Allay unites a dynamic, global team of entrepreneurs, scientists, clinicians and innovators in the San Francisco Bay Area and Singapore. Learn more at allaytx.com. View source version on businesswire.com: Contacts For further details: Investors Adam Gridley adam.gridley@allaytx.com Media Chris Railey chris@tenbridgecommunications.com M: +1 617-834-0936 Source: Allay Therapeutics View this news release online at:

SHANGHAI, Oct. 10, 2023 /PRNewswire/ -- GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, today announced the first subject was dosed in a phase Ib/II trial of GFH009 (a highly selective CDK9 inhibitor) treating relapsed/refractory PTCL (peripheral T-cell lymphomas) patients. Designed to enroll a total of 95 patients, this multi-center (close to 40 hospitals in China), open-label, single-arm study will include the prominent Sun Yat-Sen University Cancer Center and the First Affiliated Hospital of Zhengzhou University. The phase I, multi-center trial of GFH009 monotherapy for relapsed/refractory hematological malignancies has completed its dose escalation portion in both China and the US. Preliminary results demonstrated favorable safety/tolerability and promising clinical efficacy of GFH009. Complete or partial responses were observed in acute myeloid leukemia and lymphoma patients; 4 PTCL patients were observed with clinical response including one in a continuous treatment for over 48 weeks. The recommended phase II dose (RP2D) has been determined to be 100 mg once per week based on all safety, pharmacokinetics, pharmacodynamics, and efficacy data. There are approximately 100,000 newly diagnosed non-Hodgkin's lymphoma（NHL）patients per year in China, with PTCL patients accounting for over 20% of new cases. Within the histologically and clinically heterogeneous group of PTCL, patients in most subtypes (other than ALK-positive ALCL patients) are relatively chemo-resistant and are less responsive to autologous stem cell transplants. There is significant room for improvement in terms of prognosis and overall survival rate in recurrent/refractory PTCL patients after first-line treatment. Based on current studies, the functional dependence on MCL1 and the amplification or copy-number gain of MYC observed in many PTCL cell lines are correlated to poor prognosis. Clinical trials of GFH009 demonstrated significant reduction in the expression of proto-oncogenes such as MYC, MCL1, and PCNA in patients with hematological malignancies including PTCL. "GFH009 is GenFleet's first clinical-stage asset for hematological malignancies in a global multi-center trial. Currently there is significant unmet medical need in recurrent/refractory PTCL; studies from GFH009 have confirmed its potential in combating the disease. Following on GFH009's favorable safety profile and preliminary efficacy in phase I trial, we are planning to explore more studies of GFH009 monotherapy and combination therapies for global patients." stated Yu Wang, M.D., Ph.D., Chief Medical Officer of GenFleet. GenFleet received IND approval in 2020 for the GFH009 monotherapy (NCT04588922) to proceed into phase I trial treating patients with relapsed/refractory hematological malignancies. In 2022, GenFleet and SELLAS Life Sciences Group (Nasdaq: SLS) entered into an exclusive license agreement across all therapeutic and diagnostic uses. Conducted by SELLAS, the phase IIa clinical trial of SLS009 (GFH009) with venetoclax and azacitidine is ongoing in the US treating r/r AML patients. References: 1. Targeting CDK9 with selective inhibitors or degraders in tumor therapy: an overview of recent developments, 2023, Cancer Biology & Therapy 2. Current status and progress of lymphoma management in China, 2018, International Journal of Hematology 3. SELLAS Announces First Patient Dosed in Phase 2a Clinical Trial of GFH009 in Acute Myeloid Leukemia, 2023 4. VIP152, a Selective CDK9 Inhibitor, Induces Complete Regression in a High-Grade B-Cell Lymphoma Model and Depletion of Short-Lived Oncogenic Driver Transcripts, MYC and MCL1, with a Once Weekly Schedule, 2021, Blood About CDK9 and GFH009 As a family of serine & threonine kinases, the cyclin-dependent kinase (CDK) family plays an important role in cell cycle regulation and transcription; CDK9 activity is inversely correlated with the overall survival rate of patients with multiple tumors. Data from phase I trial and the preclinical research of GFH009 were posted at the 2002 Annual Meeting of the American Society of Hematology. GFH009 monotherapy is well tolerated with preliminary clinical activity in patients with relapsed/ refractory lymphomas and an AML patient observed with complete remission (with no minimal residual disease) lasting for over 8 months. According to preclinical research, GFH009 reduces the expression of downstream oncogenes required for rapid cellular division and protein expression through specific inhibition of CDK9. With more than 100 times selectivity over other CDK subtypes, this depletion via GFH009 inhibition of CDK9 likely deprives oncogene-addicted cancer cells of crucial survival signals, leading to senescence and death. GFH009 also exhibits strong anti-proliferative activities in multiple human cell lines, effectively inhibits the growth of tumor in various xenograft models and significantly improves survival of tumor bearing animals. About PTCL (peripheral T-cell lymphomas) The incidence of PTCL in Asia is substantially higher compared with western countries. The most common PTCL subtypes in China include NK/T-cell lymphoma (NKTCL), PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL). Currently, CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP with etoposide remain the most commonly used first-line treatment for PTCL. Autologous stem cell transplantation (AUTO-HSCT) may follow as a consolidation therapy for eligible patients. Based on retrospective studies, ALK-positive ALCL patients have the most favorable prognosis after applying CHOP-based regimens. However, the prognosis of relapsed/refractory PTCL patients was poor, and the median overall survival was less than 6 months. In recent years, the development of targeted drugs provided new options for patients with relapsed and refractory PTCL. About GenFleet Therapeutics GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies, is dedicated to serving significant global unmet medical needs in oncology and immunology. Based on the deep understanding of disease biology and translational medicine, GenFleet's proprietary and fully integrated R&D platform highlights multiple cutting-edge products with novel mechanisms and global IP. Since its inception in 2017, GenFleet has built up industry-leading capabilities and expertise in developing novel drug candidates - both small molecules and biologics. Its pipeline includes over 10 programs, many of which have entered multi-regional clinical trials across China (including Taiwan region), the United States, Europe and Australia. To date, GenFleet has over 5 clinical studies encompassing IND stage to phase II studies and completed co-development partnerships with numerous publicly listed companies worldwide. GenFleet is expected to progress additional programs into the clinic, as well as transition from a clinical stage biotech company into a commercial stage biopharmaceutical company in the next 3-5 years. SOURCE GenFleet Therapeutics

The drug was developed by researchers at the City of Hope, one of the largest cancer research and treatment organizations in the US, over a 20-year period. The AOH1996 molecule targets a cancerous variant of PCNA, a protein critical to DNA replication and repair of enlarging tumors. It has shown to be effective in preclinical research treating cells derived from breast, prostate, brain, ovarian, cervical, skin and lung cancers The research, published in the journal Cell Chemical Biology, tested the treatment across over 70 cancer cell lines. The results found that AOH1996 selectively kills cancer cells by ‘disrupting the normal cell reproductive cycle’. It targets transcription replication conflicts, which occur when mechanisms responsible for gene expression and genome duplication collide . ​ The investigational therapy prevented cells with damaged DNA from dividing in G2/M phase and from making a copy of faulty DNA in S phase. As a result, AOH1996 caused cancer cell death (apoptosis), but it did not interrupt the reproductive cycle of healthy stem cells. However, while early results are promising, the research so far has only been conducted with cell and animal models – with a phase 1 human trial currently underway. Professor Linda Malkas, senior author of the new drug study, said: "PCNA is like a major airline terminal hub containing multiple plane gates. Data suggests PCNA is uniquely altered in cancer cells, and this fact allowed us to design a drug that targeted only the form of PCNA in cancer cells." googletag.cmd.push(function () { googletag.display('text-ad1'); }); “Our cancer-killing pill is like a snowstorm that closes a key airline hub, shutting down all flights in and out only in planes carrying cancer cells. Results have been promising. AOH1996 can suppress tumor growth as a monotherapy or combination treatment in cell and animal models without resulting in toxicity. The investigational chemotherapeutic is currently in a phase 1 clinical trial in humans at City of Hope." Professor Long Gu, lead author of the study, added: “No one has ever targeted PCNA as a therapeutic because it was viewed as 'undruggable,' but clearly City of Hope was able to develop an investigational medicine for a challenging protein target. “We discovered that PCNA is one of the potential causes of increased nucleic acid replication errors in cancer cells. Now that we know the problem area and can inhibit it, we will dig deeper to understand the process to develop more personalized, targeted cancer medicines."