On June 3, 2022 Bristol Myers Squibb (NYSE:BMY) and Turning Point Therapeutics, Inc. (NASDAQ:TPTX) reported a definitive merger agreement under which Bristol Myers Squibb will acquire Turning Point Therapeutics for $76.00 per share (Press release, Turning Point Therapeutics, JUN 3, 2022, View Source [SID1234615500]). The transaction was unanimously approved by both the Bristol Myers Squibb and Turning Point Therapeutics Boards of Directors and is anticipated to close during the third quarter of 2022.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Turning Point Therapeutics is a clinical-stage precision oncology company with a pipeline of investigational medicines designed to target the most common mutations associated with oncogenesis. Turning Point Therapeutics’ lead asset, repotrectinib, is a next-generation, potential best-in-class tyrosine kinase inhibitor (TKI) targeting the ROS1 and NTRK oncogenic drivers of non-small cell lung cancer (NSCLC) and other advanced solid tumors. Repotrectinib has been granted three Breakthrough Therapy Designations from the U.S. Food and Drug Administration. 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.

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. The company also plans to continue to explore the potential of Turning Point Therapeutics’ promising pipeline of novel compounds.

"The acquisition of Turning Point Therapeutics further broadens our leading oncology franchise by adding a best-in-class, late-stage precision oncology asset," said Giovanni Caforio, M.D., Board Chair and Chief Executive Officer, Bristol Myers Squibb. "With this transaction, we are continuing our strong track record of strategic business development to further enhance our growth profile."

"Today’s news builds upon our long legacy of pioneering next-generation medicines for patients with cancer," said Samit Hirawat, M.D., Chief Medical Officer, Global Drug Development, Bristol Myers Squibb. "With repotrectinib, we have the opportunity to change the standard of care and address a significant unmet medical need for ROS1-positive non-small cell lung cancer patients."

"Through this transaction, we will be able to harness the full potential of our precision oncology platform to advance the standard of care for cancer patients. Since our founding, we have leveraged our deep scientific expertise to develop a pipeline of promising precision oncology assets," said Athena Countouriotis, M.D., President and Chief Executive Officer, Turning Point Therapeutics. "With Bristol Myers Squibb’s leadership in oncology, strong commercial capabilities and manufacturing footprint, we will be able to further accelerate the pace at which we can bring our novel medicines to benefit people diagnosed with cancer around the world."

Financial Details and 2022 Financial Guidance

The transaction supports Bristol Myers Squibb’s medium- to long-term growth strategy with accretion to non-GAAP earnings per share (EPS) beginning in 2025. The transaction is expected to be up to $0.08 per share dilutive to non-GAAP EPS in 2022 prior to any impact from an acquired in-process research and development charge based on final accounting treatment. The accounting treatment as a business combination or asset acquisition will be determined upon the expected close of the transaction in the third quarter of 2022.

Transaction Terms and Financing

Under the terms of the merger agreement, Bristol Myers Squibb will promptly commence a tender offer to acquire all of the outstanding shares of Turning Point Therapeutics’ common stock at a price of $76.00 per share in an all-cash transaction for a total consideration of $4.1 billion in equity value. Turning Point Therapeutics’ Board of Directors unanimously recommends that Turning Point Therapeutics shareholders tender their shares in the tender offer.

The transaction is subject to customary closing conditions, including the tender of a majority of the outstanding shares of Turning Point Therapeutics’ common stock and the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. Following the successful closing of the tender offer, Bristol Myers Squibb will acquire all remaining shares of Turning Point Therapeutics that are not tendered into the tender offer through a second-step merger at the same price of $76.00 per share.

Bristol Myers Squibb expects to finance the acquisition with cash on hand.

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.

On June 3, 2022 IconOVir Bio, Inc. (IconOVir), a preclinical-stage biotechnology company pioneering the next generation of oncolytic virus (OV) therapy to improve the treatment of patients with cancer, reported that Mark McCamish, M.D., Ph.D., President and Chief Executive Officer of IconOVir, will present a corporate overview at the Jefferies Healthcare Conference on Friday, June 10, 2022 at 8:00 a.m. ET (5:00 a.m. PT) in New York, NY (Press release, IconOVir Bio, JUN 3, 2022, View Source [SID1234615496]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On June 3, 2022 Precision BioSciences, Inc. (Nasdaq: DTIL) a clinical stage gene editing company developing ARCUS-based ex vivo allogeneic CAR T and in vivo gene editing therapies, reported that the Company will share an update on its allogeneic CAR T programs during a company-hosted webcast and conference call on June 8, 2022 at 8:00 AM ET (Press release, Precision Biosciences, JUN 3, 2022, View Source [SID1234615495]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We look forward to sharing the recent developments on our CAR T programs, including the latest clinical data on our potential first-in-class allogeneic CAR T program, PBCAR0191, in patients who relapsed following CAR T treatment," said Alan List, M.D., Chief Medical Officer at Precision BioSciences. "The CAR T relapse setting is a rapidly growing area with dire unmet medical need that is not adequately addressed by current treatment options."

Company-Hosted Webcast and Conference Call Information

Precision will host a conference call and webcast on Wednesday, June 8, 2022 at 8:00 AM ET to review its ongoing allogeneic CAR T programs. The dial-in conference call numbers for domestic and international callers are (866) 996-7202 and (270) 215-9609, respectively. The conference ID number for the call is 5754683. Participants may access the live webcast, and accompanying presentation materials, as well as the archived webcast on Precision’s website in the Investors section under Events & Presentations: View Source

On June 3, 2022 ALX Oncology Holdings Inc., ("ALX Oncology") (Nasdaq: ALXO) a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, reported clinical program updates for its lead program, evorpacept, a next generation CD47 blocker (Press release, ALX Oncology, JUN 3, 2022, View Source [SID1234615494]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Introducing ASPEN-07, a Phase 1 Trial of Evorpacept for the Treatment of Patients with Urothelial Carcinoma ("UC")

ALX Oncology will initiate a new clinical study, ASPEN-07, to investigate evorpacept in combination with an antibody-drug conjugate ("ADC"), PADCEV (enfortumab vedotin-ejfv), for the treatment of patients with urothelial carcinoma ("UC") in the fourth quarter of 2022.
Enfortumab vedotin-ejfv is an ADC directed to Nectin-4, a protein located on the surface of cells that is highly expressed in UC.
In April 2022, ALX Oncology successfully completed a pre-IND consultation with the U.S. Food and Drug Administration ("FDA") for a Phase 1 study of evorpacept in combination with enfortumab vedotin-ejfv in patients with previously treated locally advanced or metastatic UC.
The IND application for ASPEN-07 was submitted to the FDA in May 2022.
"We continue to pursue strategies to expand the potential value of evorpacept as a cornerstone therapy for the treatment of patients with cancer," said Jaume Pons, Ph.D., Founder, President and Chief Executive Officer of ALX Oncology. "ASPEN-07 further expands our solid tumor investigations and will be the first combination study of evorpacept with an ADC. The addition of evorpacept is expected to enhance the antibody-dependent cellular phagocytosis mediated by enfortumab vedotin-ejfv to improve efficacy in patients with UC without increasing toxicity. Our currently enrolling randomized Phase 2 studies remain a key priority for us in order to maintain ALX Oncology’s leadership position in solid tumors in the CD47 space."

Update of ASPEN-05, a Phase 1 / 2 Clinical Trial of Evorpacept in Combination with Venetoclax and Azacitidine in Acute Myeloid Leukemia ("AML"), and ASPEN-02, a Phase 1/2 Study of Evorpacept in Combination with Azacitidine in Myelodysplastic Syndrome ("MDS")

The Phase 1 dose escalation portion of ASPEN-05 has successfully completed enrollment with no safety concerns to date up to the highest protocol defined dose level of 60 mg/kg evorpacept once every four weeks. This portion of the study is designed to characterize the initial safety of evorpacept in combination with venetoclax and azacitidine for the treatment of patients with relapsed/refractory AML and previously untreated AML who are not candidates for intensive induction therapy.
Patient enrollment will be paused before proceeding into the Phase 1 dose optimization portion of ASPEN-05 pending completion of the Phase 1 portion of ASPEN-02, a Phase 1/2 study of evorpacept in combination with azacitidine in patients with MDS. Data from ASPEN-02 will be used to inform the optimal dose(s) of evorpacept to be studied in the ASPEN-05 study in combination with venetoclax and azacitidine. Ongoing patients in ASPEN-05 will continue to be treated and followed per protocol.
"The decision to pause ASPEN-05 is based on the desire to leverage upcoming dose optimization data from the ASPEN-02 MDS study to effectively inform dose optimization in ASPEN-05," said Sophia Randolph, M.D., Ph.D., Chief Medical Officer of ALX Oncology. "MDS and AML are indications where evorpacept possesses a similar mechanism of action, and this strategy allows us to evaluate evorpacept in a cost-efficient manner in patients with AML while maintaining our focus in our solid tumor programs. We anticipate preliminary dose escalation data from ASPEN-05 to be presented at a scientific conference in 2022, and initial dose optimization data from ASPEN-02 to be presented at a scientific conference in mid-2023."

Update of ASPEN-03 and ASPEN-04, which are two distinct randomized Phase 2 studies for the treatment of patients with advanced head and neck squamous cell carcinoma ("HNSCC")

ALX Oncology continues to advance evorpacept in two randomized Phase 2 studies in patients with HNSCC in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, with or without chemotherapy. Both studies are being conducted in collaboration with Merck, known as MSD outside the United States and Canada. The first study, ASPEN-03, is evaluating the efficacy of evorpacept in combination with pembrolizumab for the first-line ("1L") treatment of patients with PD-L1 expressing metastatic or unresectable, recurrent HNSCC with a Combined Positive Score ("CPS") ≥ 1. The second study, ASPEN-04, is investigating evorpacept in combination with pembrolizumab and standard chemotherapy for the 1L treatment of patients with metastatic or unresectable, recurrent HNSCC (any CPS value).
Patient enrollment for ASPEN-03 and ASPEN-04 continues as planned with results expected to be presented by mid-2024.
Update of ASPEN-06, a Phase 2/3 Study of Evorpacept for the Treatment of Patients with Advanced Gastric or Gastroesophageal Junction ("GEJ") Cancer

ASPEN-06 is a randomized Phase 2 (open-label) / Phase 3 (double-blind), international, multi-center study to evaluate the efficacy of evorpacept and CYRAMZA (ramucirumab) added to trastuzumab and paclitaxel for the treatment of patients with HER-positive gastric/GEJ cancer whose tumors have progressed following treatment with HER2-targeted therapy and chemotherapy. ASPEN-06 is being conducted in collaboration with Eli Lilly and Company.
In March 2022, the first patient was dosed in the Phase 2/3 ASPEN-06 study.
Patient enrollment continues to progress and results from the Phase 2 portion of ASPEN-06 are expected to be presented in 2023.

On June 3, 2022 Immunocore Holdings Plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infection and autoimmune disease, reported it has entered into a clinical trial collaboration and supply agreement with Sanofi (Press release, Immunocore, JUN 3, 2022, View Source [SID1234615493]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the agreement, Sanofi will evaluate its precisely PEGylated, engineered version of IL-2, SAR444245, in combination with KIMMTRAK, Immunocore’s novel bispecific protein targeting gp100, in HLA-A*02:01 positive patients with advanced unresectable or metastatic skin cancers as part of Sanofi’s ongoing Phase 1/2 study.

Under the terms of the agreement, Sanofi will be responsible for clinical development and will assume all costs associated with the study, other than expenses related to the manufacturing and supply of KIMMTRAK for which Immunocore is responsible.

SAR444245 (formerly known as THOR-707), Sanofi’s product candidate, is a differentiated IL-2 engineered for specificity and selectivity towards CD8+ T cells and Natural Killer (NK) cells. The molecule has a single, targeted PEG-moiety irreversibly linked to a novel amino acid inserted at a precise location. This characteristic prevents SAR444245 from binding to CD25 (alpha-subunit) while preferentially binding to the beta/gamma IL-2 receptor subunits. Beta/gamma IL-2 receptor engagement has tuned IL-2 specificity for the robust proliferation of T-effector and NK cells, avoiding expansion of T-regulatory cells or eosinophils.

John Reed, MD, PhD, Executive Vice President and Global Head of R&D of Sanofi, said: "We are excited to embark on this collaboration with Immunocore. The strong scientific rationale makes it compelling to investigate Immunocore’s KIMMTRAK, the first approved TCR therapeutic for a solid tumor, in combination with our engineered lymphokine, SAR444245. While we are actively studying SAR444245 as monotherapy and in combination with anti-PD-1 class checkpoint inhibitors and with approved immuno-competent monoclonal antibodies, the collaboration with Immunocore represents Sanofi’s first exploration of combining SAR444245 with a T cell engager. We are therefore very eager to explore this high potential combination in our ongoing multi-arm Phase 1/2 clinical study."

David Berman, MD, PhD, Head of Research and Development at Immunocore, said: "Immunocore has demonstrated that in vitro, IL-2 can enhance the activity of the ImmTAC platform, particularly in the context of tumor-associated inhibitory macrophages, and that metastatic uveal melanoma (mUM) patients with higher expression of IL2-beta and gamma, but not alpha, receptor have better overall survival (OS) on KIMMTRAK (presented at SITC (Free SITC Whitepaper) 2021). We are pleased that Sanofi will test this hypothesis in their clinical trial in patients with metastatic cutaneous melanoma (mCM), a population with significant unmet medical need."

In January 2022 and April 2022, the United States Food and Drug Administration (FDA) and the European Commission (EC), respectively, approved KIMMTRAK (tebentafusp) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM). Immunocore is currently planning a randomized study of KIMMTRAK with or without anti-PD1 therapy in patients with metastatic melanoma and anticipates initiating the trial in the fourth quarter of 2022.

##

About KIMMTRAK
KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognize and kill tumor cells. KIMMTRAK has been granted Breakthrough Therapy Designation, Fast Track designation and orphan drug designation by the FDA in the United States, Accelerated Assessment by the EMA, and Promising Innovative Medicine (PIM) designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma.

IMPORTANT SAFETY INFORMATION

Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS.

Skin Reactions

Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions.

Elevated Liver Enzymes

Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.

Embryo-Fetal Toxicity

KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose.

The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.

Please see full Prescribing Information, including BOXED WARNING for CRS.

About KIMMTRAKConnect
Immunocore is committed to helping patients who need KIMMTRAK obtain access via our KIMMTRAKConnect program. The program provides services with dedicated nurse case managers who provide personalized support, including educational resources, financial assistance, and site of care coordination. To learn more, visit KIMMTRAKConnect.com or call 844-775-2273.

About ImmTAC Molecules
Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune "cold" low mutation rate tumors.