On December 12, 2022 Clovis Oncology, Inc. (NASDAQ:CLVS) ("Clovis" or the Company"), a biopharmaceutical company focused on acquiring, developing, and commercializing innovative anti-cancer agents in the U.S., Europe, and additional international markets, reported that it and certain of its subsidiaries (collectively, the "Debtors") have voluntarily initiated a Chapter 11 proceeding in the United States Bankruptcy Court for the District of Delaware ("Bankruptcy Court") and will seek to sell their assets through a court supervised sales process (Press release, Clovis Oncology, DEC 12, 2022, View Source [SID1234625046]).

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The Debtors have filed various "first day" motions with the Bankruptcy Court requesting customary relief that will enable them to transition into Chapter 11 without material disruption to their ordinary course operations, including seeking authority to obtain debtor-in-possession ("DIP") financing and pay employee wages and benefits.

DIP Financing

In order to provide necessary funding during the Chapter 11 proceeding, Clovis has received a commitment of up to $75 million in a multi-draw DIP financing facility. Upon approval by the Bankruptcy Court, the DIP financing is expected to provide Clovis with the necessary liquidity to operate in the normal course and meet obligations to its employees, vendors and customers throughout the Chapter 11 proceeding while executing on the sales process.

Sales Process

Prior to the Chapter 11 filing, and subject to Bankruptcy Court approval, the Company entered into a "stalking horse" purchase and assignment agreement with Novartis Innovative Therapies AG ("Novartis") to acquire substantially all of the rights of the Company to its pipeline clinical candidate, FAP-2286, as a therapeutic agent for an upfront payment of $50 million and up to an additional $333.75 million upon the successful achievement of specified development and regulatory milestones and $297 million in later sales milestones. The transaction is part of a sale process under Section 363 of the Bankruptcy Code that will be subject to compliance with agreed upon and Bankruptcy Court-approved bidding procedures allowing for the submission of higher or otherwise better offers, and other agreed-upon conditions. In addition, the transaction is subject to customary closing conditions, including the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended. In accordance with the sale process under Section 363 of the Bankruptcy Code, notice of the proposed sale to Novartis will be given to third parties and competing bids will be solicited. The Company will manage the bidding process and evaluate any bids received, in consultation with its advisors and as overseen by the Bankruptcy Court.

Clovis is also actively engaged in discussions with a number of interested parties with respect to a potential sale of one or more of its other assets. Any of those sales would be subject to review and approval by the Bankruptcy Court and compliance with Bankruptcy Court-approved bidding procedures.

Clovis is represented by Willkie Farr & Gallagher LLP as counsel, AlixPartners LLP as restructuring advisor and Perella Weinberg Partners L.P. as restructuring investment banker.

Additional information about the Chapter 11 case, including access to Bankruptcy Court documents, is available online at View Source

On December 12, 2022 Ellipses Pharma Limited ("Ellipses"), a global drug development company focused on accelerating the development of new oncology treatments, reported that it has presented preliminary data from the first in human phase 1/2 trial of EP0042, a dual FLT-3 an Aurora kinase inhibitor, in patients with acute myeloid leukaemia (AML) at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in New Orleans, Louisiana (Press release, Ellipses Pharma, DEC 12, 2022, View Source [SID1234625044]).

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EP0042 is being developed as a new potential treatment to combat acquired resistance to FLT3 inhibitors in patients with AML. Around one third of patients with AML are diagnosed with FLT3-mutations, which are associated with a higher risk of relapse and poor clinical outcome.1 The preliminary data, from the ongoing dose ranging module of the trial, demonstrated that EP0042 had acceptable safety and tolerability with evidence of prolonged disease stabilisation in a number of heavily pre-treated patients.2 No dose-limiting toxicities were observed, and the emerging adverse event profile of EP0042 appears to be characterised by febrile neutropenia, fatigue diarrhoea, peripheral oedema, dizziness, and ataxia . The data were presented by Dr David Taussig, Consultant Haematologist at The Royal Marsden NHS Foundation Trust and Honorary Team Leader in Acute Leukaemia at the Institute for Cancer Research, during the poster session on Sunday, December 11, 2022.

The preliminary data is based upon 25 patients across 6 dose cohorts including patients with FLT3 mutated and wild type AML at the point of enrolment. The median number of prior treatments was 2 (range 1-6), with a number of patients having received a prior FLT3 inhibitor.

Once a recommended Phase-2 dose is confirmed, Ellipses intends to continue evaluating EP0042 as a monotherapy and explore EP0042 in combination with established standard treatments.

Dr David Taussig, Consultant Haematologist at The Royal Marsden NHS Foundation Trust and Chief Investigator, said:

"I am excited to lead the first in-human clinical trial of EP0042, a drug which I hope will ultimately improve outcomes of patients with AML, for whom current treatment regimens are often ineffective. I look forward to building on this early clinical data alongside my colleagues, as we take this potentially important candidate further into the clinic."

Dr Rajan Jethwa, CEO of Ellipses, said:

"Ellipses’ unique approach to drug development allows us to accelerate drugs through the clinic and shorten the amount of time it takes for vital treatments to reach cancer patients. The preliminary data from EP0042 is a first step in potentially uncovering the promise that this compound holds and ultimately helping AML patients with limited treatment options."

About EP0042

EP0042 is a dual FLT3 and Aurora kinase inhibitor under development as a potential treatment for AML patients who have developed FLT3 inhibitor resistance. Dual inhibition of FLT3 and Aurora kinase has been shown to overcome acquired resistance to selective FLT3 inhibition both in vitro and in vivo.3

About acute myeloid leukaemia

Acute myeloid leukaemia (AML) is a cancer of the bone marrow, which begins to produce excess volumes of monocytes and granulocytes. It is one of the most common types of leukaemia in adults. Approximately 20,000 people are diagnosed with AML in the US each year,4 and a further 3,100 in the UK, with around 40% of cases being diagnosed in people over the age of 75.5 The 5-year survival rate following an initial diagnosis is currently 15%

On December 11, 2022 GSK plc (LSE/NYSE: GSK) reported new 48-week data from the MOMENTUM phase III trial that showed a majority of patients treated with investigational momelotinib maintained their responses across key clinical measures including Total Symptom Score (TSS), Transfusion Independence (TI) rate, and Splenic Response Rate (SRR) in myelofibrosis patients previously treated with an approved Janus kinase (JAK) inhibitor (Press release, GlaxoSmithKline, DEC 11, 2022, View Source [SID1234625112]). Additionally, new analyses from MOMENTUM showed that TI response with momelotinib at week 24 was associated with overall survival. These data were presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (10-13 December) in New Orleans.

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Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK, said: "Myelofibrosis patients have significant medical needs including progressive anaemia resulting from the disease and often exacerbated by currently approved treatments. The data presented today reinforce the potential of momelotinib as a treatment option with a favourable impact on myelofibrosis symptoms and spleen volume, as well as on blood transfusions due to anaemia."

MOMENTUM is a global, randomised, double-blind phase III clinical trial of momelotinib (MMB) versus danazol (DAN) in patients with myelofibrosis who were symptomatic and anaemic and had been previously treated with an approved JAK inhibitor. The study was designed to evaluate the safety and efficacy of momelotinib for the treatment and reduction of the key manifestations of the disease: constitutional symptoms, blood transfusions (due to anaemia) and enlarged spleen. Patients were randomised at 2:1 to receive either momelotinib or danazol (n=130 and n=65, respectively). After 24 weeks of treatment, patients on danazol were allowed to crossover to receive momelotinib. Early crossover to momelotinib was available for confirmed splenic progression.

Primary analysis at week 24 met the primary endpoint of TSS reduction of ≥50% over the 28 days immediately before the end of week 24 compared to baseline TSS, using the Myelofibrosis Symptom Assessment Form. It also met key secondary endpoints including TI rate for ≥12 weeks immediately before the end of week 24 with haemoglobin levels ≥ 8 g/dL and SRR based on splenic volume reduction of ≥35% at week 24 from baseline.

48-week follow-up data from MOMENTUM presented at ASH (Free ASH Whitepaper) demonstrated the following (oral presentation #627):

TSS response at week 24 and maintained below baseline through week 48

TI response at week 24 and maintained response through week 48

SRR response at week 24 and maintained below baseline through week 48

MMB

31/32 (97%)*

36/40 (90%)

24/24 (100%)***

DAN with crossover to MMB at week 24

6/6 (100%)**

10/13 (77%)

2/2 (100%)

*12 of 61 (20%) non-responding patients who received momelotinib at week 24 had achieved a TSS response at week 48

**10 of 35 (29%) non-responding patients who received danazol and crossed over to momelotinib at week 24 achieved a new TSS response at week 48

***data available for 24 of 30 patients who received momelotinib and achieved splenic response at 24 weeks

In MOMENTUM, the most common Grade 3 or greater treatment emergent adverse events in the open-label period, similar to the double-blind period, were thrombocytopenia (9% for the continuous momelotinib treatment arm and 15% for the danazol to momelotinib treatment arm) and anaemia (9% for the continuous momelotinib treatment arm and 2% for the danazol to momelotinib treatment arm). Additionally, these efficacy and safety results in patients with thrombocytopenia were consistent with the overall population.

An additional analysis from the MOMENTUM clinical trial evaluated the impact of TI response on overall survival (abstract #3028). As previously presented, patients receiving treatment with momelotinib were more likely to achieve transfusion independence during the study period than patients treated with danazol (TI response at week 24 of 31% and 20% for the momelotinib and danazol arms, respectively; non-inferiority p=0.0064). Momelotinib patients were also less likely to require a transfusion during the study period (35% of momelotinib patients had zero units transfused compared to 17% of danazol patients; odds ratio=2.7; p=0.0107), and more likely to reduce transfusion burden. Data presented at ASH (Free ASH Whitepaper) with additional survival follow up suggests that TI response with momelotinib at week 24 is associated with overall survival (HR=0.27 for TI vs. non-TI; CI 95% 0.09, 0.80) compared to patients who were not TI.

A New Drug Application and Marketing Authorisation Application for momelotinib is currently under review with the US Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively. Momelotinib is not currently approved in any market.

About momelotinib
Momelotinib is an investigational oral treatment for myelofibrosis. Momelotinib not only inhibits the Janus kinase (JAK) 1 signalling pathway and JAK2 signalling pathways, but also activin A receptor type I (ACVR1).[i],[ii],[iii],[iv] Inhibition of JAK1 and JAK2 may improve constitutional symptoms and splenomegaly.[i],[ii],[iv] Additionally, direct inhibition of ACVR1 leads to a decrease in circulating hepcidin, which is often elevated in myelofibrosis and contributes to anaemia.[i],[ii],[iii],[iv]

About myelofibrosis
Myelofibrosis is a rare and potentially fatal cancer characterized by the build-up of excessive scar tissue in the bone marrow, which interferes with the production of healthy blood cells and can lead to: severe low blood counts, including anaemia and thrombocytopenia; constitutional symptoms such as weakness and fatigue; and splenomegaly or an enlarged spleen.[v],[vi],[vii] Myelofibrosis affects about 1 in 500,000 people worldwide.[viii] At diagnosis, approximately 40% of patients are anaemic and nearly all myelofibrosis patients will eventually develop anaemia.[ix],[x],[xi] Patients will often require blood transfusions, and more than 30% will discontinue treatment due to anaemia.[xii] Anaemia and transfusion dependence are strongly correlated with poor prognosis, reduced quality of life and shortened survival

On December 11, 2022 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage cell and gene therapy company advancing a new class of treatments for patients with cancer and rare diseases, reported that the Company will present preclinical data from its P-FVIII-101 gene therapy program, partnered with Takeda, at the 2022 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in New Orleans and virtually December 10–13, 2022 (Press release, Poseida Therapeutics, DEC 11, 2022, View Source [SID1234625071]). The data establish preclinical proof of principle for the treatment of Hemophilia A using P-FVIII-101, a non-viral liver-directed gene therapy utilizing Poseida’s Super piggyBac delivery system, which could potentially lead to a functional cure.

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Poseida Therapeutics (PRNewsfoto/Poseida Therapeutics, Inc.)

"We are very excited by these new P-FVIII-101 data, which demonstrate normalization of FVIII levels in an animal model of Hemophilia A," said Brent Warner, President, Gene Therapy at Poseida Therapeutics. "Most importantly, we have demonstrated the use of a fully non-viral gene therapy to address the underlying cause of Hemophilia A, providing key preclinical proof of principle for our program. We look forward to our continued work on this program together with our partner, Takeda."

Details of the oral presentation are as follows:

Title: Sustained Factor VIII Activity Following Single Dose of Non-Viral Integrating Gene Therapy
Presenter: Brian Truong, Ph.D.
Presentation Date and Time: Today, December 11, 2022 at 10:15 AM CT
Session Name: 321. Coagulation and Fibrinolysis: Basic and Translational
Publication Number: 400
Location: Ernest N. Morial Convention Center, 293-294

P-FVIII-101 utilizes the Company’s non-viral, nanoparticle-based delivery system together with SPB, which enables increased transgene cargo capacity, stable integration into the genome, potential for re-dosing, and potentially simpler manufacturing processes. The data to be presented show that P-FVIII-101 achieved and sustained normalized (>50%) hFVIII activity following a single dose and delivered therapeutic FVIII activity in mice following single and repeat doses, indicating the potential for dose titration. Durable responses were observed following a single dose reported over the study period of seven months. The data support that with SPB the therapeutic transgene expression cassette can be stably integrated into the genome of liver cells and provide consistent and durable therapeutic activity.

"Although gene therapy has the potential to deliver functional cures for Hemophilia A, current approaches face challenges – both with durability and the ability to re-dose – and are not appropriate for use in juvenile patients," said Denise Sabatino, Ph.D., Research Associate Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP) and an author on the oral presentation. "The data being presented today show that P-FVIII-101 has the potential to correct a deficiency in FVIII to near normal levels in juvenile mice, providing a path forward for a more tolerable, durable treatment for Hemophilia A in pediatric patients. Current treatment options are not curative and require lifelong treatment, and P-FVIII-101 may have the potential to significantly improve outcomes for people with Hemophilia A."

In October 2021, Poseida announced that it had entered into a research collaboration and exclusive license agreement with Takeda to utilize the Company’s proprietary genetic engineering platform technologies for the research and development of gene therapies, including P-FVIII-101. The companies plan to continue preclinical studies to advance the program toward an Investigational New Drug (IND) application.

About P-FVIII-101
P-FVIII-101 is a liver-directed gene therapy partnered with Takeda combining Poseida’s Super piggyBac platform and nanoparticle delivery technologies for the in vivo treatment of Hemophilia A. Hemophilia A is a bleeding disorder caused by a deficiency in Factor VIII production with a high unmet need. P-FVIII-101 utilizes the piggyBac gene integration system delivered via lipid nanoparticle, which has demonstrated stable and sustained Factor VIII expression in animal models.

On December 11, 2022 Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immuno-oncology company developing novel T cell engagers, reported updated interim data from its Phase 1 clinical trial evaluating single-agent HPN217 in relapsed/refractory multiple myeloma (RRMM) in a poster presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held in person and virtually in New Orleans (Press release, Harpoon Therapeutics, DEC 11, 2022, View Source [SID1234625070]). HPN217 targets B-cell maturation antigen (BCMA) and is based on Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC) platform designed to recruit a patient’s own immune cells to kill tumor cells.

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The interim results, as of the data cut-off date of October 17, 2022, showed that HPN217 demonstrated continued evidence of clinical activity and a tolerable safety profile in heavily pre-treated patients with RRMM (62 patients treated across fixed dose and step dose regimens). HPN217 was active across a wide dose range (2.15 to 24 mg), with 77% (10/13) ORR observed across the highest step doses (12 and 24 mg). A majority of responders had decreases in the serum BCMA biomarker (sBCMA, a marker correlated with disease prognosis) by week two of treatment. Additionally, 86% (18/21) of responders remain on study treatment with sustained response, with many responders on treatment for over a year. Three patients in the study were evaluated for minimal residual disease (MRD), and all three were MRD negative (<10-5). sBCMA remained undetectable at 9 months in many responders who achieved very good partial response (VGPR) or better.

Low-grade CRS occurred in 29% of patients across the highest step dose regimens (12% Grade 1 and 18% Grade 2) and was seen primarily in the earliest doses. No Grade 3 or higher CRS or any immune effector cell associated neurotoxicity syndrome (ICANS) events have been observed.

"The encouraging initial clinical activity with deepening and durable responses observed in patients who have received multiple prior lines of therapy, combined with a generally well-tolerated safety profile, suggest the investigational T cell engager HPN217 may offer meaningful clinical benefits for patients with relapsed/refractory multiple myeloma," said Al-Ola A. Abdallah, M.D., of University of Kansas Medical Center, a Principal Investigator in this study. "I look forward to continuing to study this promising drug candidate in these patients with advanced disease for whom there remains a significant unmet need for new treatment options."

"These data provide further validation of our proprietary TriTAC T cell engager platform, demonstrating robust clinical activity for HPN217 at higher doses, while maintaining tolerability in this heavily refractory patient population," said Luke Walker, M.D., Chief Medical Officer of Harpoon Therapeutics. "These data support our continued clinical development efforts, and we look forward to continuing dose optimization with ongoing patient enrollment in the Phase 1 trial expected to reach completion in the first half of 2023."

For more details about the ASH (Free ASH Whitepaper) Annual Meeting, please visit: View Source

The poster (publication #3240) will be available on Harpoon’s website following today’s presentation.

Conference Call and Webcast Details

Harpoon’s management will host a live call/webcast on Monday, December 12, 2022, at 4:30 ET/3:30 CT/1:30 PT, to review the interim results of its Phase 1 HPN217 clinical program and provide an update on other pipeline programs. The live call may be accessed by dialing 1-877-407-9039 for domestic callers and 1-201-689-8470 for international callers with conference ID code number 13734677. A live webcast of the call will be available from the Events and Presentations section of Harpoon’s website here and will be archived there shortly after the live event.

About HPN217

HPN217 targets B-cell maturation antigen (BCMA) and is based on Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC) platform designed to recruit a patient’s own immune cells to kill tumor cells.

In November 2019, Harpoon Therapeutics and AbbVie announced a licensing agreement and option to advance HPN217 and expand an existing discovery collaboration. Under the terms of the agreement, AbbVie may exercise its option to license HPN217 after completion of the Phase 1 clinical trial.

In March 2022, the FDA granted Fast Track designation to HPN217, underscoring its potential to address a serious unmet medical need for patients with relapsed, refractory multiple myeloma.

About the HPN217 Clinical Trial

HPN217 is being evaluated in an ongoing Phase 1, multicenter, open-label dose escalation study designed to evaluate safety, tolerability, pharmacokinetics (PK) and clinical activity in patients with relapsed/refractory multiple myeloma who have had at least three prior systemic treatments, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody, including patients with prior exposure to BCMA therapy. Primary objectives are characterization of safety, tolerability, PK and determination of the recommended Phase 2 dose.

As of the cutoff date on October 17, 2022, maximum tolerated dose has not yet been reached in the step-dose regimen. Assessment of the Q2 cohort dosing schedule is ongoing.

For additional information about the trial, please visit www.clinicaltrials.gov using the identifier NCT04184050.