On June 27, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported topline results from the TACTI-003 (KEYNOTE-PNC-34) Phase IIb trial evaluating eftilagimod alfa (efti) in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma patients (1L HNSCC) (Press release, Immutep, JUN 27, 2024, View Source [SID1234644556]). The trial enrolled 171 patients with any PD-L1 expression (Combined Positive Score [CPS] ≥1) and negative PD-L1 expression (CPS <1) at over 30 centres across the United States, Europe, and Australia.

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Topline Results – overall trial, primary endpoint
Immutep’s MHC Class II agonist in combination with KEYTRUDA led to higher overall response rates in evaluable patients according to RECIST 1.1 – the primary endpoint of the study – across all levels of PD-L1 expression (CPS >20, CPS 1-19, CPS >1, CPS <1) as compared to KEYTRUDA monotherapy (see Table 1). In the overall evaluable TACTI-003 patient population (Cohort A and B), the response rate for efti in combination with KEYTRUDA was ~34% regardless of HPV status and PD-L1 expression, including patients with negative PD-L1 expression.

Dr. Martin Forster of the UCL Cancer Institute and University College London Hospital NHS Foundation, London, UK, and TACTI-003 Investigator, stated, "It is encouraging to see efti safely drive higher response rates in combination with KEYTRUDA in the first line setting for head and neck squamous cell carcinoma patients, regardless of HPV status and levels of PD-L1. The strong, consistent response rates, irrespective of whether patients have high, low, or negative PD-L1 expression, is intriguing and offers a glimpse into this novel combination’s ability to improve patients’ clinical responses and expand patient populations that benefit from anti-PD-1 therapy."

Cohort A results – randomised part of trial
In the randomised, controlled Cohort A (N=138; thereof 118 evaluable) comprised of 1L HNSCC patients with any PD-L1 expression (CPS >1), the novel immuno-oncology (IO) combination shows the strongest outperformance in patients with high PD-L1 expression (CPS >20) with a 31.0% overall response rate (ORR) and 75.9% disease control rate (DCR) in evaluable patients (N=29) as compared to a 18.5% ORR and 59.3% DCR for KEYTRUDA monotherapy in evaluable patients (N=27). High PD-L1 expressing patients represent ~50% of the overall population in 1L HNSCC.

The IO combination also achieved a relatively high ORR of 34.5% in evaluable patients (N=29) with low PD-L1 expression (CPS 1-19). The ORR with KEYTRUDA monotherapy in patients with low PD-L1 expression in TACTI-003 (N=33) was 33.3% and is higher than historical published data for pembrolizumab monotherapy, including a 14.5% ORR in patients with CPS 1-19 in a registrational study1. The large difference of the control arm versus historical results in low PD-L1 patients may be explained by imbalances between the TACTI-003 treatment groups, including smoker status and location of primary tumour.

Cohort B results
The Company is also pleased to report that the response rate in patients with negative PD-L1 expression (CPS <1) in Cohort B has substantially improved from the preliminary 26.9% ORR reported in April and that the updated clinical data has been accepted for an ESMO (Free ESMO Whitepaper) Virtual Plenary session. ESMO (Free ESMO Whitepaper) Virtual Plenaries are monthly presentations of the latest, original scientific data, including "Phase II trials which demonstrate remarkable therapeutic benefit, scientific insight or progress in an area of unmet need". Final topline results including complete response rate in patients with negative PD-L1 expression, who represent ~20% of the overall population in 1L HNSCC, will be delivered via an oral presentation on 11 July 2024. This cohort was not randomised due to ethical reasons as KEYTRUDA monotherapy is not approved for these patients.

Safety
With respect to safety, the profile of efti in combination with KEYTRUDA continues to be favourable with no new safety signals as expected.

Dr. Frédéric Triebel, CSO of Immutep, said: "We are pleased with the quality of responses. Once again, durability is tracking well driven by the complementary nature of these two unique immunotherapies in fighting cancer. Efti’s distinct activation of dendritic cells as an MHC Class II agonist and the resulting engagement of multiple facets of the adaptive & innate immune system has consistently translated into promising duration of responses in combination with immune checkpoint inhibitors across multiple oncology indications. From a statistical point of view, given the relatively small number of evaluable patients and the very ambitious differences required to generate significance, coupled with unexpected imbalances leading to unanticipated strength in the control arm among patients with low PD-L1 expression, we are excited to see the ~68% differential in the largest patient segment (CPS >20) in 1L HNSCC in a randomised setting."

"Additionally, the strength of clinical results in patients with negative PD-L1 expression is notable, and we look forward to sharing more data at the ESMO (Free ESMO Whitepaper) Virtual Plenary session in July," added Dr. Triebel.

Next Steps
Based on these positive topline results, the Company will discuss potential options with regulatory agencies for metastatic 1L HNSCC patients. More detailed clinical data from TACTI-003 will be presented at a medical conference in H2 CY2024.

Conference Call and Webcast Details
Immutep will host a conference call and webcast to discuss the clinical data. The event will feature CEO Marc Voigt, CSO Dr Frederic Triebel, CMO Dr Florian Vogl, and Christian Mueller, Senior Vice President Strategic Development. An open question & answer session with all presenters will conclude the event. A replay of the webcast will be available under the Events section of Immutep’s website.
• Date/Time: Thursday, 27 June, at 9AM AEST (Wednesday, June 26, at 7PM ET)
• Register: Link to register for webcast
• Questions: Investors are invited to submit questions in advance via [email protected]

Efti has received FDA Fast Track designation in 1L HNSCC regardless of PD-L1 expression.
KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About the TACTI-003 Trial
The TACTI-003 (KEYNOTE-PNC-34) trial is an ongoing Phase IIb study evaluating eftilagimod alfa (efti), Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist, in combination with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The randomized Cohort A portion of the study is evaluating efti in combination with pembrolizumab as compared to pembrolizumab monotherapy in patients with PD-L1 positive (Combined Positive Score [CPS] ≥1) tumours, whereas Cohort B is evaluating efti in combination with pembrolizumab in patients with PD-L1 negative tumours.

The primary endpoint of the study is Overall Response Rate of evaluable patients according to RECIST 1.1. Secondary endpoints include Overall Survival, Overall Response Rate according to iRECIST, Progression Free Survival, and Duration of Response. For more information about the Phase IIb trial, visit clinicaltrials.gov (NCT04811027).

About Eftilagimod Alfa (Efti)
Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track designation in first line HNSCC and in first line NSCLC from the United States Food and Drug Administration (FDA).

On Jun 27, 2024 Genmab A/S (Nasdaq: GMAB) reported that the U.S. Food and Drug Administration (FDA) has approved EPKINLY (epcoritamab-bysp) for the treatment of adults with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy (Press release, Genmab, JUN 27, 2024, View Source [SID1234644555]). With this approval, EPKINLY is the first and only T-cell engaging bispecific antibody administered subcutaneously approved in the U.S. to treat this patient population. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial(s).

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FL is the second most common form of non-Hodgkin’s lymphoma (NHL), accounting for 20-30 percent of all NHL cases.i About 15,000 people develop FL each year in the U.S.ii FL is considered incurable with current standard of care therapies and patients often relapse.iii,iv With each subsequent line of therapy, patients receiving currently available treatments may experience shorter durability of response.v

"Patients with relapsed or refractory follicular lymphoma face significant treatment challenges, especially in third-line settings where there is currently no clear standard of care treatment," said Jeff Sharman, MD, Disease Chair, Hematology Research, Sarah Cannon Research Institute (SCRI) at Willamette Valley Cancer Institute in Eugene, Oregon. "This approval and the durable responses observed in the follicular lymphoma cohort of the EPCORE NHL-1 clinical trial, which reflected a real-world patient population, including patients with difficult-to-treat follicular lymphoma, demonstrate the potential of EPKINLY for patients who face limited therapeutic options post-relapse."

The approval is based on results from the phase 1/2 EPCORE NHL-1 clinical trial, which evaluated the safety and preliminary efficacy of EPKINLY in 127 adult patients with R/R FL who previously received a median of three lines of therapy and with 70% having double refractory disease. The results showed an overall response rate (ORR) of 82% and a complete response (CR) rate of 60%, including 67% of patients achieving minimal residual disease (MRD) negativity. Additionally, more than half of patients who responded to treatment in the study remained responsive to treatment at the time of data analysis (i.e., at a median follow-up of 14.8 months, median duration of response (DoR) was not reached). The study included prespecified subgroups representing patients with challenging-to-treat FL, including patients who were refractory to both anti-CD20 therapy and an alkylating agent, patients who were refractory to last prior treatment, and patients whose disease progressed within two years of first-line immunochemotherapy (POD24). These results were recently published in the Lancet Haematology.

Common treatment-emergent adverse events (TEAEs) (≥20%) from the FL cohort of the trial were injection site reaction, cytokine release syndrome (CRS), COVID-19, fatigue, upper respiratory tract infection, musculoskeletal pain, rash, diarrhea, fever, cough, and headache. For patients who received EPKINLY at the recommended 3 step-up dosage schedule, CRS was primarily low grade (40% Grade 1, 9% Grade 2). There were no grade 3 CRS events observed. The prescribing information has a Boxed Warning for serious or life-threatening CRS and immune effector cell-associated neurotoxicity syndrome (ICANS). Warnings and precautions include infections, cytopenias, and embryo-fetal toxicity. Please see additional Important Safety Information below.

"With this approval, patients whose follicular lymphoma has relapsed or is refractory to at least two or more lines of systemic therapy, now have the option to be treated with EPKINLY, which has demonstrated durable responses without mandatory hospitalization using a 3 step-up dosage regimen in this patient population in clinical trials," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "In just over a year, EPKINLY has received a second indication in the U.S., making it the first and only bispecific antibody approved to treat patients with diffuse large B-cell lymphoma and follicular lymphoma after two or more lines of systemic therapy. The approved indications, along with the ongoing clinical development program, underscore the potential of epcoritamab to become a core therapy across B-cell malignancies."

"People living with follicular lymphoma are in need of additional options when their cancer returns," said Lee Greenberger, Ph.D., Chief Scientific Officer at The Leukemia & Lymphoma Society. "Today’s approval is welcome news for patients, as it provides another tool in the physician arsenal for this difficult-to-treat form of cancer."

NCCN Clinical Practice Guidelines
The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for "B-Cell Lymphomas" were recently updated (Version 2.2024) to add EPKINLY as a Category 2A, preferred recommendation for third-line and subsequent therapy for patients with FL. This recommendation is based on uniform NCCN consensus that the intervention is appropriate.vi

About the EPCORE NHL-1 Trial
EPCORE NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a dose escalation part; an expansion part; and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (B-NHL), including FL. In the expansion part, additional patients were enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-NHLs who have limited therapeutic options. The expansion part generated pivotal data from patients with FL and DLBCL. The optimization part evaluated additional CRS mitigation strategies during cycle 1. The primary endpoint of the expansion part was overall response rate as assessed by an Independent Review Committee. Secondary efficacy endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were also evaluated as secondary efficacy endpoints. The primary endpoint of the optimization part was the rate of ≥ Grade 2 CRS events and all grade CRS events from first dose of epcoritamab through 7 days following administration of the second full dose of epcoritamab.

About Follicular Lymphoma (FL)
FL is typically an indolent (or slow-growing) form of non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes.vii Although FL is an indolent lymphoma, it is considered incurable with conventional therapy and patients who achieve remission also often experience relapse.iii,iv,viii Additionally, with each relapse the remission and time to next treatment is shorter.ix,x

About EPKINLY (epcoritamab-bysp)
EPKINLY is a prescription medicine used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, or follicular lymphoma (FL) that has come back or that did not respond to previous treatment after receiving 2 or more treatments. EPKINLY is approved based on patient response data. Studies are ongoing to confirm the clinical benefit of EPKINLY. It is not known if EPKINLY is safe and effective in children.

Epcoritamab is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.xi

Epcoritamab (approved under the brand name EPKINLY in the U.S. and Japan, and TEPKINLY in the EU) has received regulatory approval in certain lymphoma indications in several territories. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization.

Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes four ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigators choice chemotherapy (NCT04628494), a trial evaluating epcoritamab in combination with R-CHOP in adult participants with newly diagnosed DLBCL (NCT05578976), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) in patients with R/R FL (NCT05409066), and a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) compared to chemoimmunotherapy in patients with previously untreated FL (NCT06191744). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit www.clinicaltrials.gov for more information.

EPKINLY (epcoritamab-bysp) U.S. IMPORTANT SAFETY INFORMATION

Important Warnings—EPKINLY can cause serious side effects, including:

Cytokine release syndrome (CRS), which is common during treatment with EPKINLY and can be serious or life-threatening. To help reduce your risk of CRS, you will receive EPKINLY on a step-up dosing schedule (when you receive 2 or 3 smaller step-up doses of EPKINLY before your first full dose during your first cycle of treatment), and you may also receive other medicines before and for 3 days after receiving EPKINLY. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule.
Neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY.
People with DLBCL or high-grade B-cell lymphoma should be hospitalized for 24 hours after receiving their first full dose of EPKINLY on day 15 of cycle 1 due to the risk of CRS and neurologic problems.

Tell your healthcare provider or get medical help right away if you develop a fever of 100.4°F (38°C) or higher; dizziness or lightheadedness; trouble breathing; chills; fast heartbeat; feeling anxious; headache; confusion; shaking (tremors); problems with balance and movement, such as trouble walking; trouble speaking or writing; confusion and disorientation; drowsiness, tiredness or lack of energy; muscle weakness; seizures; or memory loss. These may be symptoms of CRS or neurologic problems. If you have any symptoms that impair consciousness, do not drive or use heavy machinery or do other dangerous activities until your symptoms go away.

EPKINLY can cause other serious side effects, including:

Infections that may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment and treat you as needed if you develop an infection. You should receive medicines from your healthcare provider before you start treatment to help prevent infection. Tell your healthcare provider right away if you develop any symptoms of infection during treatment, including fever of 100.4°F (38°C) or higher, cough, chest pain, tiredness, shortness of breath, painful rash, sore throat, pain during urination, or feeling weak or generally unwell.
Low blood cell counts, which can be serious or severe. Your healthcare provider will check your blood cell counts during treatment. EPKINLY may cause low blood cell counts, including low white blood cells (neutropenia), which can increase your risk for infection; low red blood cells (anemia), which can cause tiredness and shortness of breath; and low platelets (thrombocytopenia), which can cause bruising or bleeding problems.
Your healthcare provider will monitor you for symptoms of CRS, neurologic problems, infections, and low blood cell counts during treatment with EPKINLY. Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.

Before you receive EPKINLY, tell your healthcare provider about all your medical conditions, including if you have an infection, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. If you receive EPKINLY while pregnant, it may harm your unborn baby. If you are a female who can become pregnant, your healthcare provider should do a pregnancy test before you start treatment with EPKINLY and you should use effective birth control (contraception) during treatment and for 4 months after your last dose of EPKINLY. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EPKINLY. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.

In DLBCL or high-grade B-cell lymphoma, the most common side effects of EPKINLY include
CRS, tiredness, muscle and bone pain, injection site reactions, fever, stomach-area (abdominal) pain, nausea, and diarrhea. The most common severe abnormal laboratory test results include decreased white blood cells, decreased red blood cells, and decreased platelets.

In follicular lymphoma the most common side effects of EPKINLY include injection site reactions, CRS, COVID-19, tiredness, upper respiratory tract infections, muscle and bone pain, rash, diarrhea, fever, cough, and headache. The most common severe abnormal laboratory test results include decreased white blood cells and decreased red blood cells.

These are not all of the possible side effects of EPKINLY. Call your doctor for medical advice about side effects. You are encouraged to report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch or to Genmab US, Inc. at 1-855-4GENMAB (1-855-443-6622).

Please see Medication Guide, including Important Warnings.

Helping Patients Access Care
Genmab strives to positively impact the lives of patients when our medicines reach the people who need them. We understand the impact that cancer can have, and we offer support throughout the treatment journey. MyNavCare Patient Support by Genmab is available to patients in the U.S. who have been prescribed EPKINLY. MyNavCare offers resources and services, from financial information to ongoing patient support, to help eligible patients access their Genmab medication. MyNavCare provides helpful information for patients, care partners and the healthcare providers who serve those patients throughout their treatment journey. Patients, care partners and healthcare providers interested in learning more about MyNavCare can visit www.MyNavCare.com or call 1-866-NAV-CAR1 (1-866-628-2271).

On June 26, 2024 Verrica Pharmaceuticals Inc. (the "Company") reported to have entered into an amendment (the "Amendment") to its Credit Agreement dated as of July 26, 2023 (the "Credit Agreement"), by and between the Company, as borrower, OrbiMed Royalty & Credit Opportunities IV, LP, as a lender, each other lender that may from time to time become a party thereto, and OrbiMed Royalty & Credit Opportunities IV, LP, as administrative agent for the lenders (Filing, Verrica Pharmaceuticals, JUN 26, 2024, View Source [SID1234644596]). As previously disclosed, payments of the principal amount of borrowings under the Credit Agreement, together with a repayment premium and other fees, are not required under the Credit Agreement unless the Company’s net revenue attributable to YCANTHTM does not equal or exceed specified amounts for specified test periods as set forth in the Credit Agreement. Pursuant to the Amendment, the parties agreed to modify the commencement of such revenue test so that such revenue test now begins on September 30, 2024. In connection with the Amendment, the Company agreed to pay the lenders an amendment fee of $500,000.

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Except as set forth in the Amendment, the remaining terms of the Credit Agreement, as amended to date, remain unchanged. The foregoing description of the terms of the Amendment are not intended to be complete and are qualified in their entirety by reference to the Amendment, which the Company expects to file as an exhibit to the Company’s Quarterly Report on Form 10-Q for the quarter ending June 30, 2024.

On June 26, 2024, Coherus BioSciences, Inc., a Delaware corporation (the "Company"), reported to have entered into an Asset Purchase Agreement (the "Purchase Agreement") by and between the Company and Hong Kong King-Friend Industrial Company Ltd., a Hong Kong corporation ("HKF"). HKF is the parent company of Meitheal Pharmaceuticals, Inc., a Delaware corporation (Press release, Coherus Biosciences, JUN 26, 2024, View Source [SID1234644564]).

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Pursuant to the terms and subject to the conditions set forth in the Purchase Agreement, the Company agreed to divest its YUSIMRY (adalimumab-aqvh) franchise (the "Business") through the sale of certain assets, including YUSIMRY, intellectual property exclusively related to YUSIMRY, certain contracts related to YUSIMRY, YUSIMRY inventory, and all activities related to research and development of YUSIMRY, to HKF and the assumption of certain liabilities by HKF, including $17.0 million of inventory purchase commitments, but not including certain identified excluded assets and excluded liabilities (collectively, the "YUSIMRY Disposition") for upfront, all-cash consideration of $40.0 million paid on June 26, 2024.

The Purchase Agreement also provides for indemnification rights related to breaches of each party’s representations, warranties, covenants and certain other matters such as losses incurred by HKF for excluded assets or excluded liabilities or losses incurred by the Company for assumed liabilities. The indemnification obligations of each party are subject to the limitations set forth in the Purchase Agreement.

The Purchase Agreement contains customary representations, warranties and covenants related to the Company, the Business and the YUSIMRY Disposition that are subject, in some cases, to specified exceptions and qualifications contained in the Purchase Agreement. The covenants include, among other things, (a) an agreement for the Company to provide access to records related to the Business after the closing of the YUSIMRY Disposition and (b) an agreement to certain non-competition and non-solicitation agreements.

Pursuant to the Purchase Agreement, the closing of the YUSIMRY Disposition occurred on June 26, 2024.

The representations and warranties of the Company and HKF contained in the Purchase Agreement have been made solely for the benefit of the parties to the Purchase Agreement. In addition, such representations and warranties (a) have been made only for purposes of the Purchase Agreement, (b) have been qualified by confidential disclosures made to the Company and HKF in connection with the Purchase Agreement, (c) are subject to materiality qualifications contained in the Purchase Agreement which may differ from what may be viewed as material by investors, (d) were made only as of the date of the Purchase Agreement, or such other dates that are specified in the Purchase Agreement and (e) have been included in the Purchase Agreement for the purpose of allocating risk between the Company and HKF rather than establishing matters as facts. Accordingly, the Purchase Agreement is included with this filing only to provide investors with information regarding the terms of the Purchase Agreement, and not to provide investors with any other factual information regarding the Company or HKF or their respective subsidiaries, affiliates or businesses. Investors and security holders are not third-party beneficiaries under the Purchase Agreement and should not rely on the representations and warranties or any descriptions thereof as characterizations of the actual state of facts or condition of the Company or HKF or any of their respective subsidiaries, affiliates or businesses. Moreover, information concerning the subject matter of the representations and warranties may change after the date of the Purchase Agreement, which subsequent information may or may not be fully reflected in the Company’s public disclosures.

The foregoing description of the Purchase Agreement and the YUSIMRY Disposition is not complete and is qualified in its entirety by reference to the Purchase Agreement, which is filed as Exhibit 2.1 hereto and is incorporated herein by reference.

On June 26, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported positive initial data from the ongoing Phase 1 MINOTAUR clinical trial evaluating lunresertib (RP-6306) in combination with FOLFIRI in patients with advanced solid tumors (Press release, Repare Therapeutics, JUN 26, 2024, View Source [SID1234644560]). The data are being presented in a mini oral presentation by Elisa Fontana, M.D., Ph.D., Medical Director, Sarah Cannon Research Institute UK at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Gastrointestinal (GI) Cancers Congress 2024, being held June 26-29 in Munich, Germany.

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"The initial results from the ongoing MINOTAUR trial demonstrate promising efficacy and tolerability data of lunresertib plus FOLFIRI in genomically defined tumors that represent 20% of all gastrointestinal cancers," said Dr. Elisa Fontana. "These early data suggest that lunresertib plus FOLFIRI combination therapy may effectively treat patients with CCNE1 amplification and deleterious FBXW7 mutations, who often suffer from poor prognosis and lack approved treatment options. We are excited by the prolonged benefit that some patients continue to experience on therapy, especially in colorectal cancer, and the favorable tolerability of this lunresertib combination therapy across tumor types, unlike other agents combined with irinotecan."

Lunresertib is a first-in-class precision oncology small molecule PKMYT1 inhibitor that targets CCNE1 amplification, FBXW7 and PPP2R1A alterations in solid tumors. Lunresertib is being evaluated in combination with other therapies across several Phase 1 and Phase 2 clinical trials, as well as in multiple investigator-sponsored trials.

Key Initial Findings from the Phase 1 MINOTAUR Clinical Trial:

MINOTAUR (NCT05147350) is a Phase 1, multi-center, open-label, dose-scalation study to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of lunresertib in combination with FOLFIRI in advanced solid tumors. Primary objectives of the study were safety and tolerability, and determination of the recommended Phase 2 dose (RP2D) and schedule. Secondary objectives were pharmacokinetics, preliminary evidence of anti-tumor activity, pharmacodynamics, and circulating tumor DNA (ctDNA) monitoring. As of May 2, 2024, the cutoff date for the data presented at the ESMO (Free ESMO Whitepaper) GI Congress, 38 patients were enrolled in the clinical trial.

Preliminary RP2D established as 60mg BID lunresertib continuous plus standard FOLFIRI
Promising efficacy in heavily pretreated population with tumors that harbor CCNE1 amplification and FBXW7 mutation alterations
Overall response (OR) across tumor types was 18.2% (n=33), including four confirmed and two unconfirmed partial responses (PR), regardless of prior irinotecan exposure
Prolonged clinical benefit rate (CBR) across tumor types, primarily digestive system tumors, was 51.5%, including 46.7% of patients with recurrent colorectal cancer (CRC)
Patients with CRC (n=15) had prolonged duration of therapy, with 40% (2/5) of irinotecan-naïve patients and 20% (2/10) of irinotecan-experienced patients on treatment for over nine months, compared to clinical benchmarks of 20% and 5-10%, respectively
ctDNA molecular response rate was 61% among evaluable patients (14/23)
Lunresertib combination therapy was well tolerated without excess toxicity above expected rates for lunresertib or standard FOLFIRI alone
No safety-related treatment discontinuations at preliminary RP2D
Neutropenia and leukopenia were the most common Grade 3/4 treatment-related adverse events (TRAE), consistent with that reported for FOLFIRI alone and reversible with FOLFIRI interruption
Rate of low-grade, reversible rash was consistent with lunresertib monotherapy experience
"The encouraging tolerability and early antitumor efficacy data and the potential duration of treatment advantage of the combination of lunresertib plus FOLFIRI in this heavily pretreated patient population warrant further development in a randomized Phase 2 study," said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. "Lunresertib in combination with FOLFIRI has the potential to provide a new therapeutic option targeting tumors harboring CCNE1 amplification and FBXW7 mutation alterations in gastrointestinal tumors, which are known to be associated with poor prognosis and where there are currently no approved treatment options."