Bristol Myers Squibb Completes Acquisition of Turning Point Therapeutics, Expanding Precision Oncology Portfolio

On August 17, 2022 Bristol Myers Squibb (NYSE:BMY) reported that it has successfully completed its acquisition of Turning Point Therapeutics, Inc. ("Turning Point"), in an all-cash transaction (Press release, Bristol-Myers Squibb, AUG 17, 2022, View Source [SID1234618449]). With the completion of the acquisition, Turning Point shares have ceased trading on the NASDAQ Global Select Market and Turning Point is now a wholly owned subsidiary of Bristol Myers Squibb.

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"Turning Point has distinguished itself in the field of precision oncology, and this acquisition will further strengthen our leading oncology franchise," said Elizabeth Mily, Executive Vice President, Strategy & Business Development, Bristol Myers Squibb. "With Turning Point’s lead asset, repotrectinib, Bristol Myers Squibb will be positioned to address a significant unmet medical need for ROS1-positive non-small cell lung cancer patients. We look forward to bringing this promising, innovative medicine to patients in the second half of 2023."

Through the transaction, Bristol Myers Squibb gains a pipeline of investigational medicines designed to target the most common mutations associated with oncogenesis, including repotrectinib. Repotrectinib is a next-generation, potential best-in-class tyrosine kinase inhibitor targeting the ROS1 and NTRK oncogenic drivers of non-small cell lung cancer (NSCLC) and other advanced solid tumors. In the Phase 1/2 TRIDENT-1 clinical trial, longer duration of response has been observed in the landmark analysis with repotrectinib than with existing ROS1 agents in first-line NSCLC. The asset has been granted three Breakthrough Therapy Designations from the U.S. Food and Drug Administration.

Bristol Myers Squibb expects repotrectinib to be approved in the U.S. in the second half of 2023 and become a new standard of care for patients with ROS1-positive NSCLC in the first-line setting. Bristol Myers Squibb also plans to continue to explore the potential of Turning Point’s promising pipeline of novel compounds.

Bristol Myers Squibb’s previously announced tender offer for all outstanding shares of common stock of Turning Point for $76.00 per share expired at 5:00 p.m. Eastern Time on August 15, 2022. Approximately 41,896,678 shares of Turning Point common stock were validly tendered, and not validly withdrawn from the tender offer, representing approximately 84% of Turning Point’s issued and outstanding shares of common stock. In accordance with the terms of the tender offer, all shares that were validly tendered and not validly withdrawn have been accepted for payment and Bristol Myers Squibb expects to promptly pay for all such shares.

Following completion of the tender offer, Bristol Myers Squibb completed the acquisition of Turning Point through the merger of its wholly owned subsidiary, Rhumba Merger Sub Inc., with and into Turning Point, without a vote of Turning Point’s stockholders pursuant to Section 251(h) of the General Corporation Law of the State of Delaware. As a result of the merger, each share of common stock of Turning Point issued and outstanding and not tendered in the tender offer was automatically converted into the right to receive an amount in cash equal to $76.00, without interest, subject to any applicable withholding of taxes, the same price offered in the tender offer.

Turning Point shareholders can direct questions regarding the tender offer to MacKenzie Partners, Inc., the information agent for the tender offer, toll free, at 1-800-322-2885.

Advisors

Gordon Dyal & Co., LLC, is serving as the exclusive financial advisor to Bristol Myers Squibb, and Kirkland & Ellis, LLP, is serving as legal counsel. Goldman Sachs & Co., LLC, is serving as the exclusive financial advisor to Turning Point Therapeutics, and Cooley, LLP, is serving as legal counsel.

Blueprint Medicines Announces Positive Top-line Results from PIONEER Trial of AYVAKIT® (avapritinib) in Patients with Non-Advanced Systemic Mastocytosis Achieving Primary and All Key Secondary Endpoints

On August 17, 2022 Blueprint Medicines Corporation (NASDAQ: BPMC) reported positive top-line results from the registrational Part 2 of the PIONEER clinical trial of AYVAKIT (avapritinib) in patients with non-advanced systemic mastocytosis (SM) demonstrating clinically meaningful and highly significant improvements across the primary and all key secondary endpoints, including patient-reported symptoms and objective measures of mast cell burden (Press release, Blueprint Medicines, AUG 17, 2022, View Source [SID1234618448]). Based on these top-line data, Blueprint Medicines plans to submit a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for AYVAKIT in non-advanced SM in the fourth quarter of 2022, with a subsequent submission of a type II variation marketing authorization application to the European Medicines Agency (EMA) anticipated in 2023. In addition, Blueprint Medicines plans to present detailed data from the PIONEER trial at an upcoming medical meeting.

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The trial, which was designed to assess AYVAKIT plus best available care versus placebo plus best available care (control arm), achieved its primary endpoint with a highly significant difference in the mean change in total symptom score (TSS) at 24 weeks (p=0.003). TSS was assessed by the Indolent SM Symptom Assessment Form (ISM-SAF). The AYVAKIT arm had a reduction of 15.6 points in mean TSS at 24 weeks, which continued to deepen to 20.2 points at 48 weeks in patients who rolled over to the Part 3 open-label extension study. At 24 weeks, the control arm had a reduction of 9.2 points in mean TSS. In addition, the PIONEER trial met all key secondary endpoints, including significant improvements across all measures of mast cell burden. More than half of AYVAKIT-treated patients had a ≥50 percent reduction of serum tryptase, compared to no patients in the control arm (53.9% vs. 0%; p<0.0001). AYVAKIT was well-tolerated and had a favorable safety profile, and 96.5 percent of AYVAKIT-treated patients completed 24 weeks of therapy, compared to 93.0 percent for the control arm. Overall, 0.7 percent of patients in the AYVAKIT arm and no patients in the control arm discontinued due to treatment-related adverse events.

"As a physician and clinical researcher who has been treating non-advanced systemic mastocytosis patients for over 25 years, I have been awaiting a therapy that decreases the abnormal mast cell burden and activation, improves a wide range of symptoms, and ultimately provides an improved quality of life to patients," said Mariana Castells, M.D., Ph.D., Director, Mastocytosis Center, Brigham and Women’s Hospital, and an investigator on the PIONEER trial. "For patients with non-advanced SM, PIONEER is the first study to show significant clinical improvements over best available care across patient-reported symptoms and objective measures of disease, with a safety and tolerability profile supporting chronic treatment. The trial results suggest that if approved, AYVAKIT would represent a practice-changing treatment, enabling important clinical benefits for a broad range of patients with non-advanced SM."

"The PIONEER results showcase Blueprint Medicines’ dedication to advancing the promise of precision therapy for patients with significant medical needs," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "AYVAKIT has the potential to be the first approved medicine for non-advanced SM, and the only treatment that would address the genetic root cause across advanced and non-advanced forms of the disease. Today’s milestone represents a watershed moment for the systemic mastocytosis community and Blueprint Medicines, capping a decade of collaboration with clinicians, advocates and patients to transform standards of care, and to deepen the understanding of this disease and its impact on various aspects of patients’ lives."

AYVAKIT was designed to potently and selectively inhibit D816V mutant KIT, the driver of SM in about 95 percent of cases. SM often leads to debilitating skin, gastrointestinal, neurocognitive and other systemic symptoms, such as life-threatening anaphylaxis.

"Non-advanced systemic mastocytosis is a lifelong disease with severe physical, emotional and social impacts that profoundly reduce patients’ quality of life," said Lauren Denton, Executive Director of The Mast Cell Disease Society. "Patients with SM continue to be challenged by efforts to avoid various triggers of everyday life while also managing complex therapies. The PIONEER clinical trial results offer hope to these patients and help pave the way for new innovation in treatment."

"These new data are the culmination of a dedicated long-term collaboration and shared ‘patients first’ core value between Blueprint Medicines and The Mast Cell Disease Society. We are excited by these results and further energized to work together with these exceptional investigators to transform the lives of patients, offering them a better quality of life and the gift of time," said Valerie Slee, Board Chair of The Mast Cell Disease Society.

Top-line Data from the PIONEER Trial

Part 2 of the registrational PIONEER trial was designed to evaluate the efficacy and safety of AYVAKIT (25 mg once-daily dosing; N=141) versus control (N=71) over 24 weeks of treatment. Eligibility criteria include an indolent SM diagnosis confirmed by central pathology review, and moderate-to-severe symptom burden despite an optimized regimen of best available care. Patients were able to continue symptom-directed therapies while receiving AYVAKIT or placebo. Results were reported as of a data cutoff date of June 23, 2022.

Baseline data, including mean TSS, were consistent with Part 1 of the trial. The PIONEER study achieved its primary endpoint and all key secondary endpoints, with AYVAKIT showing highly significant improvements in patient-reported symptoms and objective measures of disease burden.

Clinical Outcome Measures: AYVAKIT Arm vs. Control Arm P-valuea
Primary Endpoint Mean Change in TSS p=0.003
Secondary Endpointsb

≥30% Reduction in Mean TSS p=0.009
≥50% Reduction in Mean TSS p=0.005
Mean Change in Most Severe Symptom Score p=0.015
≥50% Reduction in Serum Tryptase p<0.0001
≥50% Reduction in KIT D816V Variant Allele Fraction p<0.0001
≥50% Reduction in Bone Marrow Mast Cell Aggregates p<0.0001

a One-sided p-value <0.025 indicates statistical significance.

b For secondary endpoints, reductions in TSS and objective measures of mast cell burden represent proportion of patients with ≥30% and ≥50% reductions. All endpoints are key secondary endpoints, except for mean change in most severe symptom score, which is an additional secondary endpoint.

AYVAKIT had a favorable safety profile compared to the control arm. The rate of adverse events (AEs) was 90.8 percent in the AYVAKIT arm and 93.0 percent in the control arm. Serious AEs occurred in 5.0 percent of AYVAKIT-treated patients, compared to 11.3 percent of patients in the control arm. Discontinuations due to treatment-related AEs occurred in 0.7 percent of AYVAKIT-treated patients and 0 percent of patients in the placebo arm. The AYVAKIT arm had a lower rate of cognitive AEs than the control arm (2.8% AYVAKIT vs. 4.2% control), and there were no intracranial bleeding events. Treatment-related AEs reported in at least three patients in either arm and at least 5 percent of AYVAKIT-treated patients included headache (7.8% AYVAKIT vs. 9.9% control), nausea (6.4% AYVAKIT vs 8.5% control), peripheral edema (6.4% AYVAKIT vs. 1.4% control) and periorbital edema (6.4% AYVAKIT vs. 2.8% control). In the AYVAKIT arm, 93.0 percent of edema AEs were Grade 1 and the remainder were Grade 2.

Conference Call Information

Blueprint Medicines will host a live conference call and webcast at 8:00 a.m. ET today to discuss the top-line data from the PIONEER trial. The conference call may be accessed by dialing 844-200-6205 (domestic) or 929-526-1599 (international), and referring to conference ID 806215. A webcast of the call will also be available under "Events and Presentations" in the Investors & Media section of the Blueprint Medicines website at View Source The archived webcast will be available on the Blueprint Medicines website approximately two hours after the conference call and will be available for 30 days following the call.

About AYVAKIT (avapritinib)

AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA for the treatment of adults with Advanced SM, including aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL), and adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. For more information, visit AYVAKIT.com. This medicine is approved in Europe (AYVAKYT) for the treatment of adults with ASM, SM-AHN or MCL, after at least one systemic therapy, and adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. Please click here to see the full U.S. Prescribing Information for AYVAKIT, and click here to see the European Summary of Product Characteristics for AYVAKYT.

AYVAKIT/AYVAKYT is not approved for the treatment of any other indication in the U.S. or Europe. The FDA granted breakthrough therapy designation to AYVAKIT for the treatment of moderate to severe indolent SM.

To learn about ongoing or planned clinical trials, contact Blueprint Medicines at [email protected] or 1-888-BLU-PRNT (1-888-258-7768). Additional information is available at blueprintclinicaltrials.com or clinicaltrials.gov.

About Systemic Mastocytosis

Systemic mastocytosis (SM) is a rare disease primarily driven by the KIT D816V mutation. Uncontrolled proliferation and activation of mast cells result in chronic, severe and often unpredictable symptoms for patients across the spectrum of SM. The vast majority of those affected have non-advanced (indolent or smoldering) SM, with debilitating symptoms that lead to a profound, negative impact on quality of life. A minority of patients have advanced SM, which encompasses a group of high-risk SM subtypes including ASM, SM-AHN and MCL. In addition to mast cell activation symptoms, advanced SM is associated with organ damage due to mast cell infiltration and poor survival. Across advanced SM subtypes, the median overall survival is approximately 3.5 years in ASM, approximately two years in SM-AHN and less than six months in MCL.

Debilitating symptoms, including anaphylaxis, maculopapular rash, pruritis, diarrhea, brain fog, fatigue and bone pain, often persist across all forms of SM despite treatment with a number of symptom-directed therapies. Patients often live in fear of severe, unexpected symptoms, have limited ability to work or perform daily activities, and isolate themselves to protect against unpredictable triggers. Historically, there had been no approved therapies for the treatment of SM that selectively inhibit D816V mutant KIT.

About the PIONEER Trial

PIONEER is a randomized, double-blind, placebo-controlled, registrational trial evaluating AYVAKIT in patients with non-advanced SM. The trial includes three parts: dose-finding Part 1, registrational Part 2 and long-term treatment Part 3. Key trial endpoints include the change in patient-reported disease symptoms as measured by the ISM-SAF TSS, patient-reported quality of life, quantitative measures of mast cell burden and safety. Patients who completed Part 1 or 2 were eligible to participate in Part 3. All patients receive AYVAKIT treatment during Part 3, including those rolling over from the control arm. For more information about the PIONEER trial, please visit www.clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03731260).

Atomwise Signs Strategic Multi-Target Research Collaboration with Sanofi for AI-Powered Drug Discovery

On August 17, 2022 Atomwise, a leader in using artificial intelligence (AI) for small molecule drug discovery, reported that it has established a strategic and exclusive research collaboration with Sanofi that will leverage its AtomNet platform for computational discovery and research of up to five drug targets (Press release, Atomwise, AUG 17, 2022, View Source [SID1234618447]).

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The Atomwise approach shifts the mode of drug discovery away from serendipitous discovery and toward search based on structure, making the drug discovery process more rational, effective, and efficient. The AtomNet platform incorporates deep learning for structure-based drug design, enabling the rapid, AI-powered search of Atomwise’s proprietary library of more than 3 trillion synthesizable compounds.

"At Sanofi, we are committed to bringing higher quality medicines to patients faster, empowered by our advanced AI drug discovery engine. We are excited to partner with Atomwise, given their leadership in the field of virtual screening and AI-based molecular design," said Frank Nestle, Global Head of Research and Chief Scientific Officer at Sanofi. "Together, we aim at making the drug discovery process more efficient and effective in particular when very limited information is available to support drug design."

As part of this agreement, Sanofi will pay Atomwise $20 million upfront to identify, synthesize, and advance lead compounds for up to five targets which will be exclusive to Sanofi. Subsequent payments pegged to key research, development, and sales milestones could total more than $1 billion. In addition, tiered royalties have been established for products developed through the collaboration.

"At Atomwise, our mission is to use our unique technology to make better medicines, faster, by unlocking targets that have been inaccessible to traditional small molecule discovery approaches," said Abraham Heifets, co-founder and CEO of Atomwise. "We are pleased to enter into this collaboration with Sanofi, which serves as continued validation of the important role that AI-powered platforms will play in accelerating the discovery of new therapies for diseases and conditions that may have gone untreated due to challenging or uncharacterized drug targets."

Abcam to Report Half Year Results on Monday, September 12, 2022

On August 17, 2022 Abcam plc (Nasdaq: ABCM; AIM: ABC) ("Abcam" or the "Company"), a global leader in the supply of life science research tools, reported that it will report its results for the 6-month period ended 30 June 2022 at 12.00 p.m. BST (7.00 a.m. EDT) on 12 September 2022 (Press release, Abcam, AUG 17, 2022, View Source [SID1234618446]).

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Following the announcement, the Company will host a live teleconference and webcast at 13:00 p.m. BST (8:00 a.m. EDT) that same day (details below).

To access the webcast, please use the following link:

View Source

The press release and the live audio webcast will also be available in the investor section of Abcam’s corporate website at corporate.abcam.com/investors/reports-presentations/. An archive will be available after the call at that same address.

Press Release: Sanofi provides update on amcenestrant clinical development program

On August 17, 2022 Sanofi reported that it is discontinuing the global clinical development program of amcenestrant, an investigational oral selective estrogen receptor degrader (SERD) (Press release, Sanofi, AUG 17, 2022, View Source [SID1234618444]). The decision is based on the outcome of a prespecified interim analysis of the Phase 3 AMEERA-5 trial evaluating amcenestrant in combination with palbociclib compared with letrozole in combination with palbociclib in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer.

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An Independent Data Monitoring Committee (IDMC) found that amcenestrant in combination with palbociclib did not meet the prespecified boundary for continuation in comparison with the control arm and recommended stopping the trial. No new safety signals were observed. Trial participants will be transitioned to letrozole in combination with palbociclib or another appropriate standard of care therapy, as determined by their physician.

The company will continue to review the data and plans to share the results with the scientific community in the future. All other studies of amcenestrant, including in early-stage breast cancer (AMEERA-6), will be discontinued.

John Reed, MD, PhD
Global Head of Research and Development at Sanofi
"While we are disappointed by this outcome, our research will further the scientific understanding of endocrine therapies in people with breast cancer. Our sincere gratitude goes to the patients, families and healthcare professionals involved in the amcenestrant clinical development program. Oncology remains a priority area for Sanofi, and we will continue to pursue transformative research to develop new medicines for people living with cancer."

In March, Sanofi announced that the Phase 2 AMEERA-3 trial had not met the primary endpoint of improving progression-free survival in patients with ER+/HER2- advanced or metastatic breast cancer.

About AMEERA-5
AMEERA-5 is a randomized, double-blind Phase 3 trial evaluating the efficacy and safety of amcenestrant in combination with palbociclib, a CDK4/6 inhibitor, in the first-line treatment of patients with ER+/HER2- advanced breast cancer. A total of 1068 patients who had not received any prior systemic anticancer therapies for advanced disease were randomized 1:1 to receive either amcenestrant or letrozole in combination with palbociclib.

About AMEERA-6
AMEERA-6 is a randomized, double-blind Phase 3 trial evaluating the efficacy and safety of amcenestrant compared with tamoxifen in patients with hormone receptor-positive early breast cancer who have discontinued adjuvant aromatase inhibitor (AI) therapy due to treatment related toxicity. The trial was initiated in partnership with the Breast International Group (BIG), the European Organization for Research and Treatment of Cancer (EORTC), and the Alliance Foundation Trials (AFT).