On April 29, 2024 Accord BioPharma, Inc., the U.S. specialty division of Intas Pharmaceuticals, Ltd., focused on the development of oncology, immunology, and critical care therapies, reported that the U.S. Food and Drug Administration (FDA) has approved HERCESSI (trastuzumab-strf), a biosimilar to Herceptin (trastuzumab), to treat HER2-overexpressing breast and gastric or gastroesophageal junction adenocarcinoma (Press release, Accord BioPharma, APR 29, 2024, View Source;drug-administration-approval-of-hercessi-trastuzumab-strf-a-biosimilar-to-herceptin-trastuzumab-for-the-treatment-of-several-forms-of-her2-overexpressing-cancer-302129508.html [SID1234642446]).

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"The approval of HERCESSI—our first biosimilar to be approved in the U.S.—marks an important milestone for Accord BioPharma in our efforts to improve access for patients," said Chrys Kokino, U.S. president of Accord. "Because breast and gastric cancers are among the most common types of cancer and cancer can have a high-cost burden for patients, there is a need to provide these patients with additional treatment options that may be more affordable, such as biosimilars."

HERCESSI is indicated for adjuvant treatment of HER2-overexpressing breast cancer, the treatment of HER2-overexpressing metastatic breast cancer, and the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. HER2 cancers in general are particularly aggressive cancer types that respond well to targeted treatment. HERCESSI works by binding to and inactivating the HER2 receptor, slowing down cell replication.

FDA approval was granted based on a comprehensive package of analytical, pre-clinical, and clinical data, which showed HERCESSI and its reference product, Herceptin (trastuzumab) are highly similar in terms of efficacy, safety, and quality. The clinical program for HERCESSI included three studies since 2015 to demonstrate pharmacokinetic (PK) comparability and clinical efficacy/safety similarity between HERCESSI and its reference product.

The studies include two Phase 1 comparative single-dose PK equivalence studies conducted in healthy volunteers (HLX02-HV01 and HLX02-HV02), and a supportive Phase 3, double-blind, randomized clinical efficacy and safety comparability study in patients with HER2-overexpressing metastatic breast cancer in combination with docetaxel (HLX02-BC01). The PK comparability and clinical efficacy/safety similarity exercised in HLX02-HV02 and HLX02-BC01 adheres to current biosimilar guidance from the FDA.

The safety profile of HERCESSI has been shown to be consistent with the safety profile for the reference product Herceptin. The data demonstrate that there are no clinically meaningful differences between HERCESSI and Herceptin in the populations studied and support biosimilarity between the two therapies.

"Our first FDA-approved biosimilar is an important achievement for our U.S. specialty business, but we’re just getting started. We aspire to deliver one of the deepest portfolios of biosimilars to patients and providers alike, and to help the U.S. health system achieve significant savings," said Binish Chudgar, vice chairman and managing director, Intas Pharmaceuticals. "Our vision to make affordable medicines available forms the bedrock of the company, and this work advances that vision to provide value and promote access for all the key stakeholders we engage along the treatment journey."

HERCESSI was approved by the FDA at a dosage of 150mg. A 420mg-strength version of HERCESSI is also in development from Accord BioPharma, with an FDA decision anticipated in Q4 2024.

HERCESSI was originally developed by Accord’s business partner Shanghai Henlius Biotech, Inc. headquartered in Shanghai, China. In 2021, Henlius granted Accord BioPharma the exclusive rights to develop and commercialize HERCESSI in the U.S. and Canada.

Mr. Jason Zhu, executive director, chief executive officer, and chief financial officer of Henlius remarked, "Henlius independently developed HLX02 (or HERCESSI in the U.S.) in accordance with the NMPA, the European Medicines Agency (EMA), the FDA, and other international biosimilar guidelines. It is Henlius’ first FDA-approved product. Our patient-centered approach has led us to unwaveringly explore high-quality, effective, affordable, and accessible treatment options, and our determination to promote HLX02 in more than 40 markets around the world is Henlius’ response to patients’ concerns. We look forward to reaching more patients in North America and providing them with more cost-effective access to high-quality biologics."

HERCESSI is the first U.S.-FDA-approved biosimilar from Accord BioPharma, which has also submitted a Biologics License Application to the FDA for biosimilar versions of pegfilgrastim, filgrastim and ustekinumab. Accord BioPharma is planning on introducing several additional biosimilars to the U.S. market during the next five years.

Boxed Warning and Additional Important Safety Information

HERCESSI (trastuzumab-strf) for injection, for intravenous use.

HERCESSI (trastuzumab-strf) is biosimilar to HERCEPTIN (trastuzumab).

WARNING: CARDIOMYOPATHY, INFUSION REACTIONS, EMBRYO-FETAL TOXICITY, and PULMONARY TOXICITY
See full prescribing information for complete boxed warning.

Cardiomyopathy: Trastuzumab products can result in subclinical and clinical cardiac failure manifesting as CHF, and decreased LVEF, with greater risk when administered concurrently with anthracyclines. Evaluate cardiac function prior to and during treatment. Discontinue HERCESSI for cardiomyopathy.

Infusion Reactions, Pulmonary Toxicity: Discontinue HERCESSI for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.

Embryo-Fetal Toxicity: Exposure to trastuzumab products during pregnancy can result in oligohydramnios, in some cases complicated by pulmonary hypoplasia and neonatal death. Advise patients of these risks and the need for effective contraception.

Cardiomyopathy

HERCESSI administration can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving trastuzumab with anthracycline-containing chemotherapy regimens.
HERCESSI can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death.
HERCESSI can also cause asymptomatic decline in LVEF by echocardiogram or MUGA scan.
Evaluate left ventricular function in all patients prior to and during treatment with HERCESSI and every 6 months for at least 2 years following completion of HERCESSI as a component of adjuvant therapy.
Discontinue HERCESSI treatment in patients receiving adjuvant therapy and withhold HERCESSI in patients with metastatic disease for clinically significant decrease in left ventricular function.
The safety of continuation or resumption of HERCESSI in patients with trastuzumab product-induced left ventricular cardiac dysfunction has not been studied.
Infusion Reactions

With trastuzumab products, serious and fatal infusion reactions have been reported. Severe reactions, which include bronchospasm, anaphylaxis, angioedema, hypoxia, and severe hypotension were usually reported during or immediately following the initial infusion.
Interrupt HERCESSI infusion for dyspnea, clinically significant hypotension, and intervention of medical therapy administered (which may include epinephrine, corticosteroids, diphenhydramine, bronchodilators, and oxygen).
Monitor patients until symptoms completely resolve.
Discontinue HERCESSI for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. Strongly consider permanent discontinuation in all patients with severe infusion reactions.
Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion include nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia.
Embryo-Fetal Toxicity

Exposure to HERCESSI during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception.
Verify the pregnancy status of females of reproductive potential prior to the initiation of HERCESSI.
Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of HERCESSI. Advise female patients to contact their healthcare provider with a known or suspected pregnancy.
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for HERCESSI treatment and any potential adverse effects on the breastfed child from HERCESSI or from the underlying maternal condition. This consideration should also take into account the trastuzumab product wash out period of 7 months.
Pulmonary Toxicity

HERCESSI administration can result in serious and fatal pulmonary toxicity, which includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions.
Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity.
Discontinue HERCESSI in patients experiencing pulmonary toxicity.
Exacerbation of Chemotherapy-Induced Neutropenia

In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving trastuzumab in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received trastuzumab and those who did not.
Most Common Adverse Reactions

The most common adverse reactions associated with trastuzumab products in the adjuvant and metastatic breast cancer (≥ 10%) are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia.
The most common adverse reactions associated with trastuzumab products in metastatic gastric cancer (≥ 10%) are neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia.
Indications
Adjuvant Breast Cancer
HERCESSI (trastuzumab-strf) is indicated for adjuvant treatment of HER2-overexpressing nodepositive or nodenegative (ER/PR-negative or with one high-risk feature) breast cancer:

as part of a treatment regimen containing doxorubicin, cyclophosphamide and either paclitaxel or docetaxel
as part of a treatment regimen with docetaxel and carboplatin
as a single agent following multi-modality anthracycline-based therapy
Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

Metastatic Breast Cancer
HERCESSI is indicated:

in combination with paclitaxel for the first-line treatment of HER2-overexpressing metastatic breast cancer
as a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease
Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

Metastatic Gastric Cancer
HERCESSI is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease.

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

Click here for full Prescribing Information, including Boxed Warnings.

On April 29, 2024 MorphoSys AG (FSE: MOR; NASDAQ: MOR) reported results for the first quarter of 2024 (Press release, MorphoSys, APR 29, 2024, View Source [SID1234642445]).

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"The proposed acquisition by Novartis is advancing steadily, and we continue to anticipate its closure in the first half of 2024. The acceptance period for the acquisition is currently underway, and both our Management Board and Supervisory Board unanimously recommend that our shareholders accept the offer and tender their shares given the highly attractive and equitable offer price," said Jean-Paul Kress, M.D., Chief Executive Officer of MorphoSys. "Utilizing its extensive resources, broad scientific experience and worldwide presence, Novartis will help maximize commercial and expedite development opportunities across our promising oncology programs."

Novartis’ Public Takeover Offer Highlights:

On February 5, 2024, MorphoSys announced the intention of Novartis BidCo AG, a wholly owned indirect subsidiary of Novartis AG (hereinafter collectively referred to as "Novartis"), to submit a voluntary public takeover offer for all outstanding MorphoSys no-par value bearer shares at an offer price of € 68.00 per share in cash, representing a total equity value of € 2.7 billion. The offer price corresponds to a premium of 94% and 142% on the volume-weighted average price during the last month and three months, respectively, as of the unaffected January 25, 2024, closing price.

On March 13, 2024, MorphoSys confirmed the receipt of antitrust clearance in Germany and Austria. Subsequently, on March 22, 2024, MorphoSys announced the receipt of U.S. antitrust clearance. As a result, all mandatory antitrust approvals for the proposed acquisition have been obtained.

On April 11, 2024, Novartis published its offer document. Following the publication of the offer document, the MorphoSys Management Board and Supervisory Board issued a joint reasoned statement, recommending that shareholders accept the offer and tender their MorphoSys shares. The acceptance period for shareholders commenced with the publication of the offer document on April 11, 2024, and will end on May 13, 2024, at 24:00 hours CEST and 18:00 hours EDT (also on May 13, 2024).

Medical Conferences Highlights:

On April 24, 2024, MorphoSys announced that new efficacy and safety data from the Phase 3 MANIFEST-2 trial of pelabresib, an investigational BET inhibitor, in combination with the JAK inhibitor ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis will be highlighted during an oral presentation on Friday, May 31, at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Additionally, new data from the Phase 2 study of tulmimetostat, an investigational next-generation dual inhibitor of EZH2 and EZH1, in patients with advanced solid tumors or hematologic malignancies will be showcased in a poster presentation at ASCO (Free ASCO Whitepaper) 2024 on Saturday, June 1.

Financial Results for the First Quarter of 2024 (IFRS):

The financial results presented for the first quarter of 2024 relate to continuing business operations of MorphoSys. Due to the announcement on February 5, 2024, of the sale and transfer of all rights worldwide related to tafasitamab to Incyte Corporation ("Incyte"), the entire tafasitamab business has been classified as discontinued operations. Consequently, the figures reported for the first quarter of 2023 were adapted due to this change in presentation.

Group Revenues: Group revenues from continued operations amounted to € 27.5 million (3M 2023: € 24.3 million). Group revenues mainly included revenues from royalties in the amount of € 27.0 million (3M 2023: € 20.9 million), Additional Group revenues from continued operations are attributable to licenses, milestones, and other sources, amounting to € 0.5 million (3M 2023: € 3.5 million).

Cost of Sales: Cost of sales in the first quarter of 2024 amounted to € 2.8 million (3M 2023: € 1.0 million). The year-on-year increase is mainly attributable to higher personnel costs.

Research and Development (R&D) Expenses: In the first quarter 2024, R&D expenses were € 85.2 million (Q1 2023: € 65.4 million). The increase consists mainly in personnel expenses resulting from probable effects of both an accelerated vesting of certain share-based compensation programs and the recognition of remuneration-related provisions following the proposed acquisition by Novartis.

Selling, General and Administrative (SG&A) Expenses: Selling expenses in the first quarter 2024 were € 18.5 million (Q1 2023: € 3.4 million). The increase in selling expenses is mainly due to the probable effects of accelerated vesting of certain share-based payment programs and the recognition of remuneration-related provisions following the proposed acquisition by Novartis. General and administrative (G&A) expenses amounted to € 185.5 million (Q1 2023: € 10.6 million). The increase in general and administrative expenses is mainly due to the probable effects of accelerated vesting of certain share-based payment programs and the recognition of remuneration-related provisions following the proposed acquisition by Novartis. Expenses resulting from external services mainly increased due to the expected transaction costs in connection with the proposed acquisition by Novartis.

Operating Loss: Operating loss amounted to € 264.4 million in the first quarter 2024 (Q1 2023: operating loss of € 56.1 million).

Consolidated Net Loss: For the first quarter 2024, consolidated net loss was € 311.0 million (Q1 2023: consolidated net loss of € 32.2 million).

Monjuvi/Minjuvi Update (Discontinued Operations):

On February 5, 2024, MorphoSys entered into a purchase agreement with Incyte to sell and transfer all rights worldwide related to tafasitamab to Incyte.

Monjuvi (tafasitamab-cxix) U.S. net product sales of US$ 6.4 million (€ 5.9 million) prior to the sale of tafasitamab to Incyte on February 5, 2024.

Minjuvi royalty revenue of € 0.6 million for sales outside of the U.S. prior the sale of tafasitamab to Incyte on February 5, 2024.

Since February 5, 2024, all research and development activities in connection with tafasitamab are in the responsibility of Incyte, and hence MorphoSys does no longer recognize research and development expenses from such activities.

Full Year 2024 Financial Guidance:

As a consequence of the sale and transfer of tafasitamab to Incyte on February 5, 2024, MorphoSys’ 2024 financial guidance published on January 30, 2024, cannot be maintained and therefore was revoked. For the time being, MorphoSys will no longer make a forecast for the gross margin or revenues from Monjuvi product sales, as no such revenues are expected to be realized this year.

For 2024, MorphoSys expects R&D expenses of € 170 million to € 185 million on a standalone basis. R&D expenses mainly represent our investments in the development of pelabresib and tulmimetostat. Selling, administrative and general expenses are expected to be between € 90 million and € 105 million on a standalone basis. Potential effects from the implementation of the Novartis takeover offer, including any first quarter 2024 related provisions and expenses associated with the change of control, are not included in this forecast. The overall forecast is subject to a number of uncertainties, including inflation and foreign currency effects.

Operational Outlook:

The following activity is planned for 2024:

Following the anticipated close of the proposed acquisition by Novartis in the first half of 2024, submit a New Drug Application for pelabresib in combination with ruxolitinib in myelofibrosis to the U.S. Food and Drug Administration (FDA) and a Marketing Authorization Application to the European Medicines Agency in the second half of 2024.
MorphoSys Group Key Figures (IFRS, end of the first quarter: March 31, 2024)

in € million Q1 2024 Q1 2023 Δ
Revenues 27.5 24.3 13 %
Royalties 27.0 20.9 29 %
Licenses, Milestones and Other 0.5 3.5 (86) %
Cost of Sales (2.8) (1.0) >100%
Gross Profit 24.7 23.3 6 %
Total Operating Expenses (289.1) (79.4) >100%
Research and Development (85.2) (65.4) 30 %
Selling (18.5) (3.4) >100%
General and Administrative (185.5) (10.6) >100%
Operating Profit / (Loss) (264.4) (56.1) >100%
Other Income 0.8 2.1 (62) %
Other Expenses (0.4) (1.8) (78) %
Finance Income 9.6 50.8 (81) %
Finance Expenses (56.8) (25.2) >100%
Income from Reversals of Impairment Losses / (Impairment Losses) on Financial Assets 0.1 0.5 (80) %
Share of Loss of Associates accounted for using the Equity Method (1.5) (2.5) (40) %
Income Tax Benefit / (Expenses) 1.6 0.0 n/a
Consolidated Net Profit / (Loss) from Continued Operations (311.0) (32.2) >100%
Consolidated Net Profit / (Loss) from Discontinued Operations (3.9) (12.2) (68) %
Earnings per Share, Basic and Diluted (in €) from continued operations (8.27) (0.94) >100%
Cash and other financial assets (end of period) 631.9 680.5 * (7) %
* Value as of December 31, 2023
Conference call

Due to the pending acquisition of MorphoSys by Novartis, MorphoSys will not be hosting its quarterly conference call and does not expect to do so in future quarters. Earnings materials are publicly available on the Investor Relations page of our website at www.morphosys.com/en/investors. Please direct any questions to MorphoSys Investor Relations using the contact information provided below.

On April 29, 2024 Terns Pharmaceuticals, Inc. ("Terns" or the "Company") (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology and obesity, reported findings from a Phase 1 study of TERN-701 in Western healthy volunteers (Press release, Terns Pharmaceuticals, APR 29, 2024, View Source [SID1234642435]). The study is an ongoing Phase 1 open-label, single ascending dose trial to evaluate the pharmacokinetics (PK), food effect, safety and tolerability of TERN-701 in healthy adults. TERN-701 is Terns’ proprietary, oral, potent, allosteric BCR-ABL inhibitor, a novel class of therapy for CML that has demonstrated superior efficacy and safety compared to traditional active-site tyrosine kinase inhibitors (TKIs).

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"We are pleased with the interim findings from this healthy volunteer study, which indicate TERN-701 can be administered once-daily (QD) with or without food at doses that achieve clinically efficacious exposures. TERN-701 has the potential to be a differentiated BCR-ABL inhibitor with advantages over asciminib, including more convenient dosing to improve treatment options and quality of life for people living with CML," said Emil Kuriakose, MD, chief medical officer at Terns Pharmaceuticals.

"We are excited to see clinical PK data continuing to support once-daily dosing and new data showing lack of food effect with TERN-701. The ability to dose with or without food is a key potential differentiator from asciminib, the only currently approved allosteric BCR-ABL inhibitor, which requires three hours of fasting with each dose, and twice-daily dosing in multiple clinical settings. We look forward to reporting interim dose escalation data from the ongoing Phase 1 CARDINAL trial in the second half of 2024," concluded Dr. Kuriakose.

The Phase 1 single-ascending dose (SAD) trial is ongoing in the United States and has enrolled 32 healthy volunteers in four dose escalation cohorts of eight participants each to evaluate PK, food effect and safety and tolerability at single doses ranging from 20 mg to 160 mg. No clinically meaningful changes or trends were observed in clinical laboratory data, vital signs or electrocardiogram (ECG) parameters at any dose level. Across the dose range administered to date, TERN-701 PK was linear with a median half-life ranging from 8 to 12 hours. At the 80 mg and 160 mg doses, TERN-701 exposures over 24 hours met or exceeded the predicted efficacious concentrations based on preclinical data1, consistent with observed clinical activity and safety at these doses in the ongoing Phase 1 study in China conducted by our partner, Hansoh Pharmaceuticals. Overall, the PK profile of TERN-701 in Western participants was generally consistent with that observed in the Phase 1 clinical study in Chinese CML patients.

Results of the food effect evaluation at 80 mg of TERN-701 showed no clinically significant differences in plasma exposures (area under curve, AUC) when dosed with a high-fat meal, relative to the fasted state. These results support potential dosing of TERN-701 with or without food, an initial differentiation for TERN-701 as a potentially best-in-class allosteric BCR-ABL inhibitor.

The Phase 1 healthy volunteer study remains ongoing and will proceed to enroll 320 mg and 400 mg dose cohorts. Terns plans to present these healthy volunteer data at an upcoming scientific conference.

Phase 1 CARDINAL Trial Design
The CARDINAL trial is a global, multicenter, open-label, two-part Phase 1 clinical trial to evaluate the safety, PK, and efficacy of TERN-701 in participants with previously treated CML. Part 1 is the dose escalation portion of the trial that will evaluate once-daily TERN-701 monotherapy in approximately 24-36 adults living with CML to be enrolled in up to five dose cohorts. Participants will have chronic phase CML with confirmed BCR-ABL and a history of treatment failure or suboptimal response to at least one second generation TKI (nilotinib, dasatinib or bosutinib). Participants who are intolerant to prior TKI treatment (including asciminib) are also allowed. The primary endpoints for Part 1 are the incidence of dose limiting toxicities (DLTs) during the first treatment cycle, and additional measures of safety and tolerability. Secondary endpoints include TERN-701 PK and efficacy assessments, such as hematologic and molecular responses as measured by the change from baseline in BCR-ABL transcript levels. The starting dose is 160 mg QD with dose escalations as high as 500 mg QD and the option to explore a lower dose of 80 mg QD.

Part 2 is the dose expansion portion of the trial that is planned to enroll approximately 40 patients, randomized to QD treatment with one of two doses of TERN-701 to be selected based on data from Part 1. The primary endpoint of the dose expansion portion of the trial is efficacy, measured by hematologic and molecular responses. Secondary endpoints include safety, tolerability and PK. The overall objective of the CARDINAL trial is to select the optimal dose(s) of TERN-701 to move forward to a potential pivotal trial in chronic phase CML.

The CARDINAL trial plans to enroll at sites in the U.S., Europe and other Terns global territories.

About TERN-701
TERN-701 is Terns’ proprietary, oral, potent, allosteric BCR-ABL inhibitor specifically targeting the BCR-ABL myristoyl pocket and is in clinical development for chronic myeloid leukemia. Allosteric inhibitors, which bind to the myristoyl-binding pocket, represent a novel treatment class for CML and have the potential to address the shortcomings of active-site TKIs, including off-target activity and limited efficacy against active site resistance mutations. TERN-701 aims to address the limitations of active-site TKIs with the goal of achieving improved tumor suppression through a combination of potent activity against BCR-ABL including a broad range of mutations and improved safety and tolerability profiles. Hansoh’s Phase 1 trial (NCT05367700) evaluating the tolerability, efficacy, and pharmacokinetics of once-daily TERN-701 (HS-10382) for CML in China is ongoing.

About Chronic Myeloid Leukemia
CML is a cancer that occurs when the blood-forming cells of the bone marrow overproduce white blood cells. In the United States, CML is an orphan indication with approximately 9,280 new cases expected to be diagnosed in 2024. Since the introduction of TKI therapy in 2001, CML has been transformed from a life-threatening disease to a life-long chronic condition for most patients. Despite improvements in outcomes with active-site targeting TKIs, many patients do not achieve long-term disease control with these therapies due to resistance or intolerance, leading patients to cycle through prior generation treatments. As a result, physicians and patients are seeking additional efficacious therapies for people whose tolerability, co-morbidity and/or drug-drug interaction profiles change over time, limiting their available treatment options, quality of life and the effectiveness of mainstay therapies. Allosteric BCR-ABL TKIs are the only class of drug to show efficacy and tolerability benefits compared with active-site TKIs, and represent an important advancement in the treatment of CML.

On April 29, 2024 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported a positive review of the ongoing Phase 3 REGAL clinical trial of galinpepimut-S (GPS) in acute myeloid leukemia (AML) by the Independent Data Monitoring Committee (IDMC) (Press release, Sellas Life Sciences, APR 29, 2024, View Source [SID1234642434]). The IDMC conducted a prespecified risk-benefit assessment of unblinded data from the study and has recommended that the trial continue without modifications, and scheduled its next meeting in June 2024, earlier than prescribed in the IDMC charter schedule to review the most up-to-date information regarding the number of events (deaths) required for triggering prespecified interim analysis.

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"We thank the IDMC members for the work and their guidance to continue the Phase 3 REGAL trial patients’ treatment without any modifications," said Angelos Stergiou, MD, ScD hc, President and Chief Executive Officer of SELLAS. "This recommendation was made based on the assessment of efficacy and safety of the accumulated data. We are pleased with the recently concluded enrollment for the study in the US, Europe, and Asia, per the predetermined statistical analysis plan, and we look forward to the interim analysis potentially later this quarter. If approved, GPS would be a promising new treatment in this severely underserved indication."

"As reported in March 2024, the REGAL Study Steering Committee reviewed the blinded study data with 66 patients discontinuing the treatment. In the trial, patients are recorded as having stopped the study treatment in cases of death for any reason, relapse, intolerable toxicity, or treatment completion. Regarding the GPS arm, we are pleased to report that we have not observed any intolerable toxicities in any patient population across all our clinical studies thus far, although toxicities are commonly observed with therapies used in the control arm. The IDMC also confirmed no safety issues in their recent review. Therefore, patients off treatment likely either relapsed or passed away, but as the study sponsor, we lack information on the actual number of events (60 events are required for interim analysis). This lies within the purview of the IDMC, which will now meet again in June and will review both efficacy and safety data from all enrolled REGAL patients (n=127) with a data cut-off date of around the end of May. At this point I would like to thank again all our global investigators who enrolled high numbers of patients with the top three enrolling countries, the US, Greece, and India, leading the way as a testament to the broad appeal of GPS."

REGAL is a Phase 3 open-label registrational clinical trial for GPS in AML patients who have achieved complete remission following second-line salvage therapy (CR2 patients). The primary endpoint is overall survival. The IDMC is an independent group of medical, scientific, and biostatistics experts who are responsible for reviewing and evaluating patient safety and efficacy data for REGAL, and for monitoring quality and overall conduct to ensure the validity, scientific and clinical merits of the study. The IDMC charter provides for periodic reviews of safety, efficacy, and futility in addition to the interim and final analyses.

On April 29, 2024 Pfizer Inc. (NYSE: PFE) reported its progress in advancing new potential standards of care in Oncology at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 31 to June 4 in Chicago (Press release, Seagen, APR 29, 2024, View Source [SID1234642433]). More than 50 abstracts, including 11 oral presentations, will be presented from Pfizer’s broadened portfolio of approved and pipeline therapies across the company’s key tumor areas and core scientific modalities, including small molecules, antibody-drug conjugates (ADCs) and bispecific antibodies.

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"We are excited to participate in our first ASCO (Free ASCO Whitepaper) Annual Meeting following the creation of Pfizer’s new Oncology organization, where we will highlight our efforts to accelerate breakthrough medicines that help people with cancer live better and longer lives," said Chris Boshoff, Chief Oncology Officer and Executive Vice President, Pfizer. "We are looking forward to key data presentations across our newly expanded portfolio, including additional evidence reinforcing the benefit of several approved medicines and promising new data from our deep and diverse pipeline."

Key research includes an oral presentation of new five-year progression-free survival (PFS) results from the Phase 3 CROWN study of LORBRENA (lorlatinib) in previously untreated anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC), which will also be featured in ASCO (Free ASCO Whitepaper)’s embargoed pre-meeting press briefing on Wednesday, May 29. Additionally, results from the Phase 3 ECHELON-3 study of ADCETRIS (brentuximab vedotin) in combination with lenalidomide and rituximab in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) will be presented for the first time in an oral late-breaking session.

Pfizer will also present Phase 1 data for several priority pipeline therapies, including oral presentations with updated results for sigvotatug vedotin (B6A; integrin beta-6 [IB6]-directed ADC) in NSCLC and data for PF-07248144, a potential first-in-class KAT6 inhibitor, in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC).

"At ASCO (Free ASCO Whitepaper), Pfizer will share important data highlighting the long-term impact of our medicines for patients, including five-year follow-up from the LORBRENA CROWN study, as well as the third Phase 3 study to demonstrate overall survival benefit for ADCETRIS in a type of lymphoma – in this case, relapsed/refractory diffuse large B-cell lymphoma," said Karin Tollefson, Chief Oncology Medical Officer, Pfizer. "We are also looking forward to sharing updated results from our pipeline, where we now have over 50 programs in development and are rapidly advancing 20 ongoing pivotal trials across our key tumor types."

Key ASCO (Free ASCO Whitepaper) Presentations

Pfizer will present data across its four tumor areas of focus at ASCO (Free ASCO Whitepaper): breast cancer, genitourinary cancer, hematology-oncology and thoracic cancers, which includes lung cancer.

Breast Cancer

In breast cancer, Pfizer will present data for two next-generation pipeline medicines for HR+/HER2- mBC: updated Phase 1/2a safety data for atirmociclib, a potential best-in-class, highly selective cyclin-dependent kinase 4 (CDK4) inhibitor currently in Phase 3 development, and an oral presentation featuring Phase 1 data for PF-07248144, a potential first-in-class KAT6 inhibitor. Additionally, data for TUKYSA (tucatinib) demonstrate its activity in previously treated HER2-mutated mBC, and new real-world evidence continues to support the value of IBRANCE (palbociclib) in HR+/HER2- mBC, including from HENRI-3, a SEER-Medicare analysis evaluating overall survival (OS) with IBRANCE plus an aromatase inhibitor (AI) versus AI alone.

Genitourinary Cancer

Highlights from Pfizer’s genitourinary cancer portfolio will include updated data that continue to reinforce the potential of several recent priority launches, including PADCEV (enfortumab vedotin-ejfv) in combination with KEYTRUDA (pembrolizumab) in locally advanced/metastatic urothelial cancer,* XTANDI (enzalutamide) in non-metastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high-risk for metastasis,** and TALZENNA (talazoparib) in combination with XTANDI in metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) mutations. Additionally, updated Phase 1 data will be presented for the investigational enhancer of zeste homolog 2 (EZH2) inhibitor mevrometostat in combination with XTANDI in mCRPC; Pfizer anticipates initiating Phase 3 studies for this combination later this year.

Hematology-Oncology

In addition to the ECHELON-3 OS results for ADCETRIS in relapsed/refractory DLBCL, Pfizer will present seven-year OS results for ADCETRIS in advanced classical Hodgkin lymphoma,*** as well as new clinical and pharmacokinetic data with alternative dosing regimens for ELREXFIO (elranatamab-bcmm) in relapsed/refractory multiple myeloma from the MagnetisMM-9 trial.

Thoracic Cancer

In its thoracic portfolio, in addition to the LORBRENA CROWN results, Pfizer will present updated Phase 1 data for sigvotatug vedotin in advanced NSCLC, a promising investigational ADC that recently initiated a Phase 3 study.

Additional Tumor Types

An oral presentation on extended duration of response from the Phase 3 MOUNTAINEER trial adds to the positive profile of TUKYSA in colorectal cancer. In addition, data will be presented from the innovaTV 301 trial of TIVDAK (tisotumab vedotin-tftv), for which a supplemental Biologics License Application for the treatment of previously treated recurrent or metastatic cervical cancer was granted priority review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act date of May 9, 2024.****

Additional information on key Pfizer-sponsored abstracts, including date and time of presentation, follow in the chart below. A complete list of Pfizer-sponsored accepted abstracts is available here.

Pfizer is continuing its commitment to help non-scientists understand the latest findings with the development of abstract plain language summaries (APLS) for company-sponsored research being presented at ASCO (Free ASCO Whitepaper), which are written in non-technical language. Those interested in learning more can visit www.Pfizer.com/apls to access the summaries starting Friday, May 24.

BREAST CANCER

Oral Presentation (Abstract 3006)

Saturday, June 1, 3:00-6:00 PM CDT

A phase 1 dose expansion study of a first-in-class KAT6 inhibitor — (PF-07248144) in patients with advanced or metastatic ER+ HER2− breast cancer

Mukohara et al

Poster Presentation (Abstract 3108)

Saturday, June 1, 9:00 AM-12:00 PM CDT

First-in-human phase 1/2a study of the first-in-class, next-generation CDK4-selective inhibitor PF-07220060 + endocrine therapy (ET): Updated safety data in patients with HR+/HER2− mBC

Giordano et al

Poster Presentation (Abstract 1111)

Sunday, June 2, 9:00 AM-12:00 PM CDT

Overall survival with palbociclib (PAL) plus an aromatase inhibitor (AI) versus AI alone in older patients (pts) with de novo, HR+/HER2− metastatic breast cancer: A SEER-Medicare analysis

Brufsky et al

Poster Presentation (Abstract 1105)

Sunday, June 2, 9:00 AM-12:00 PM CDT

Tucatinib and trastuzumab for previously treated HER2-mutated metastatic breast cancer (SGNTUC-019): A phase 2 basket study

Okines et al

GENITOURINARY CANCER

Oral Presentation (Abstract 4502)

Monday, June 3, 8:00-11:00 AM CDT

Patient-reported outcomes (PROs) from a randomized, phase 3 trial of enfortumab vedotin plus pembrolizumab (EV+P) versus platinum-based chemotherapy (PBC) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC)

Gupta et al

Oral Presentation (Abstract 4503)

Monday, June 3, 8:00-11:00 AM CDT

Impact of exposure on outcomes with enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer

Petrylak et al

Oral Presentation (Abstract 5005)

Saturday, June 1, 3:00-6:00 PM CDT

EMBARK post-hoc analysis of impact of treatment suspension (TxS) on health-related quality of life (HRQoL)

Freedland et al

Poster Presentation (Abstract 5021)

Sunday, June 2, 9:00 AM-12:00 PM CDT

Discovery of a novel non-negative matrix factorization (NMF)-based homologous recombination deficiency (HRD) score and subsequent exploration in TALAPRO-2 (TP-2), a phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA as first-line treatment in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)

Fizazi et al

Poster Presentation (Abstract 5061)

Sunday, June 2, 9:00 AM-12:00 PM CDT

Phase 1 trial of mevrometostat (PF-06821497), a potent and selective inhibitor of enhancer of zeste homolog 2 (EZH2), in castration-resistant prostate cancer (CRPC)

Schweizer et al

Poster Presentation (Abstract 5063)

Sunday, June 2, 9:00 AM-12:00 PM CDT

Matching-adjusted indirect comparisons (MAICs) of talazoparib plus enzalutamide (TALA+ENZA) versus olaparib plus abiraterone and prednisone/prednisolone (OLAP+AAP) for first-line (1L) therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair mutations (HRRm)/BRCAm

Castro et al

Poster Presentation (Abstract 4562)

Sunday, June 2, 9:00 AM-12:00 PM CDT

Enfortumab vedotin (EV) with pembrolizumab (P) versus chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC): Analysis of cisplatin (cis)-eligible population from EV-302/KEYNOTE-A39

Bedke et al

Poster Presentation (Abstract 4563)

Sunday, June 2, 9:00 AM-12:00 PM CDT

Enfortumab vedotin (EV) with pembrolizumab (P) versus chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC): Analysis of the cisplatin (cis)-ineligible population from EV-302/KEYNOTE-A39

Van Der Heijden et al

HEMATOLOGY-ONCOLOGY

Oral Presentation (Abstract LBA7005)

Saturday, June 1, 3:00-6:00 PM CDT

Brentuximab vedotin in combination with lenalidomide and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma: Results from the phase 3 ECHELON-3 study

Kim et al

Poster Presentation (Abstract 7053)

Monday, June 3, 9:00 AM-12:00 PM CDT

Seven-year overall survival analysis from ECHELON-1 study of A+AVD versus ABVD in patients with previously untreated stage III/IV classical Hodgkin lymphoma

Ansell et al

Poster Presentation (Abstract 7522)

Monday, June 3, 9:00 AM-12:00 PM CDT

Evaluation of cytokine release syndrome (CRS) in patients with relapsed or refractory multiple myeloma (RRMM) receiving step-up priming doses and longer dosing intervals of elranatamab: MagnetisMM-9

Sborov D

THORACIC CANCER

Oral Presentation (Abstract LBA8503)

Friday, May 31, 2:45-5:45 PM CDT

Lorlatinib vs crizotinib in treatment-naïve patients with advanced ALK+ non-small cell lung cancer: 5-year progression-free survival and safety from the CROWN study

Solomon et al

Rapid Oral Presentation (Abstract 8521)

Saturday, June 1, 4:30-6:00 PM CDT

Efficacy and safety of sigvotatug vedotin, an investigational ADC, in NSCLC: Updated phase 1 results (SGNB6A-001)

Peters et al

GYNECOLOGICAL CANCER

Poster Presentation (Abstract 5531)

Monday, June 3, 9:00 AM-12:00 PM CDT

Tisotumab vedotin in 2L/3L recurrent or metastatic cervical cancer: subsequent therapy data from ENGOT-cx12/GOG-3057/innovaTV 301

Manso Sánchez et al

GASTROINTESTINAL CANCER

Oral Presentation (Abstract 3509)

Monday, June 3, 1:15-2:45 PM CDT

Final results of a phase 2 study of tucatinib and trastuzumab for HER2-positive mCRC (MOUNTAINEER)

Strickler et al

*Pfizer and Astellas have a clinical collaboration agreement with Merck to evaluate the combination of PADCEV and KEYTRUDA in patients with previously untreated metastatic urothelial cancer.

**XTANDI is jointly developed and commercialized by Pfizer and Astellas in the United States.

***Pfizer and Takeda jointly develop ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs. Pfizer has U.S. and Canadian commercialization rights, and Takeda has rights to commercialize ADCETRIS in the rest of the world.

****TIVDAK is co-owned by Genmab and Pfizer, under an agreement in which the companies share costs and profits for the product on a 50:50 basis.

Prescribing Information for Pfizer Medicines

Please see full Prescribing Information , including BOXED WARNING, for ADCETRIS (brentuximab vedotin).

Please see full Prescribing Information, including BOXED WARNING, for ELREXFIOTM (elranatamab-bcmm).

Please see full Prescribing Information for IBRANCE (palbociclib) tablets and IBRANCE (palbociclib) capsules.

Please see full Prescribing Information for LORBRENA (lorlatinib).

Please see full Prescribing Information , including BOXED WARNING, for PADCEV (enfortumab vedotin).

Please see full Prescribing Information for TUKYSA (tucatinib).

Please see full Prescribing Information for TALZENNA (talazoparib).

Please see full Prescribing Information, including BOXED WARNING, for TIVDAK (tisotumab vedotin-tftv).

Please see full Prescribing Information for XTANDI (enzalutamide).