On May 9, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the Phase 3 KEYNOTE-B21 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy as adjuvant treatment, with or without radiotherapy, did not meet its primary endpoint of disease-free survival (DFS) for the treatment of patients with newly diagnosed, high-risk endometrial cancer after surgery with curative intent (Press release, Merck & Co, MAY 9, 2024, View Source [SID1234643004]).

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!

At a pre-specified interim analysis conducted by an independent Data Monitoring Committee, adjuvant treatment with KEYTRUDA plus chemotherapy, with or without radiotherapy, did not meet the study’s pre-specified statistical criteria for DFS compared to placebo plus adjuvant chemotherapy, with or without radiotherapy. The study’s other primary endpoint of overall survival (OS) was not formally tested since superiority was not reached for DFS. The safety profile of KEYTRUDA was consistent with that observed in previously reported studies; no new safety signals were identified. A full evaluation of the data from this study is ongoing. Merck will work with investigators to share the results with the scientific community.

"While these results were not what we had hoped, we are focused on continuing to build on the established role of KEYTRUDA in advanced endometrial carcinoma through our approved indications, while rapidly progressing clinical research evaluating KEYTRUDA-based combinations and other investigational candidates, including antibody-drug conjugates, in endometrial and other types of gynecologic malignancies," said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. "We would like to thank all the patients, the investigators and our study collaborators for their participation in this trial."

In the U.S., KEYTRUDA has two approved indications in endometrial cancer. One indication, based on KEYNOTE-775/Study 309, is in combination with LENVIMA (lenvatinib), in collaboration with Eisai, for the treatment of patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. The second indication, based on KEYNOTE-158, is as a single agent, for the treatment of patients with advanced endometrial carcinoma that is MSI-H or mismatch repair deficient (dMMR), as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Merck has a comprehensive clinical development program in endometrial carcinoma, including the NRG-GY018/KEYNOTE-868 trial evaluating KEYTRUDA in combination with standard of care chemotherapy (carboplatin and paclitaxel), followed by KEYTRUDA as a single agent for the treatment of patients with primary advanced or recurrent endometrial carcinoma. As previously announced, the U.S. Food and Drug Administration (FDA) has granted priority review for Merck’s supplemental Biologics License Application (sBLA) based on this study and has set a Prescription Drug User Fee Act (PDUFA), or target action, date of June 21, 2024.

The program also includes the KEYNOTE-C93 study evaluating KEYTRUDA versus chemotherapy in dMMR advanced or recurrent endometrial carcinoma, as well as the MK-2870-005 study evaluating sacituzumab tirumotecan (sac-TMT), an investigational trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate (ADC) being developed in collaboration with Kelun-Biotech, compared to a treatment of physicians’ choice in patients with endometrial carcinoma who have received prior platinum-based chemotherapy and immunotherapy.

About KEYNOTE-B21/ENGOT-en11/GOG-3053
KEYNOTE-B21, also known as ENGOT-en11/GOG-3053, is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT04634877) sponsored by Merck and conducted in collaboration with the European Network for Gynecologic Oncology Trial (ENGOT) groups and the GOG Foundation, Inc. (GOG) investigating adjuvant treatment with KEYTRUDA plus chemotherapy, with or without radiotherapy, compared to adjuvant placebo plus chemotherapy, with or without radiotherapy, for the treatment of newly diagnosed, high-risk endometrial cancer after surgery with curative intent. The primary endpoints are DFS and OS, and secondary endpoints include safety. The trial enrolled an estimated 1,095 patients who were randomized to receive:

KEYTRUDA (200 mg every three weeks for six cycles) plus concurrent standard of care chemotherapy (for four or six cycles), followed by KEYTRUDA (400 mg every six weeks for an additional six cycles), with or without radiotherapy, or
Placebo (every three weeks for six cycles) plus concurrent standard of care chemotherapy (for four or six cycles), followed by placebo (every six weeks for an additional six cycles), with or without radiotherapy.
About endometrial carcinoma
Endometrial carcinoma begins in the inner lining of the uterus, which is known as the endometrium, and is the most common type of cancer in the uterus. In the U.S., it is estimated there will be approximately 67,880 patients diagnosed with uterine body cancer and approximately 13,250 patient deaths from the disease in 2024. Globally, endometrial cancer is the sixth most common cancer in women and the 15th most common cancer overall. Following primary treatment, patients face a risk of their cancer returning, often as distant metastasis, which is associated with poorer outcomes.

On May 9, 2024 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of cancer and other serious diseases, reported financial results for the first quarter ended March 31, 2024 and provided a review of recent clinical and business highlights (Press release, Xencor, MAY 9, 2024, View Source [SID1234643020]).

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 have focused our XmAb clinical pipeline and discovery activities on bispecific CD3 and CD28 T cell engagers, which continue to show clinical validation for their potential in treating patients with serious diseases. Our key clinical-stage oncology programs in solid tumors include XmAb819 (ENPP3 x CD3) in clear cell renal cell carcinoma, XmAb808 (B7-H3 x CD28) in prostate cancer and other cancers, and XmAb541 (CLDN6 x CD3) in ovarian cancer and other cancers, which are all now advancing in Phase 1 clinical studies. We plan to select our next T cell engager IND candidate later this year," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "Additionally, Xencor’s best-in-class Xtend antibody half-life extension technology continues to support improved outcomes for patients, with Ultomiris now approved in the U.S. for certain patients with NMOSD, and we are especially delighted by recently published results demonstrating an investigational antibody with Xtend was effective in preventing malaria."

Recent Clinical and Business Highlights
•First Patient Dosed in Phase 1 Study of XmAb541 (CLDN6 x CD3): XmAb541 is a bispecific antibody being developed for patients with CLDN6-positive tumors including advanced ovarian cancer. XmAb541 is designed to engage the immune system, activating T cells for highly potent and targeted killing of tumor cells expressing Claudin-6 (CLDN6), a tumor-associated antigen. Xencor’s XmAb 2+1 multivalent format used in XmAb541 enables greater selectivity for cells expressing CLDN6 over similarly structured Claudin family members, which may be expressed on normal tissue. The first patient was recently dosed in a Phase 1 dose-escalation study.

•FDA Approves Ultomiris (Alexion Pharmaceuticals, Inc.) for Adults with NMOSD: In March 2024, Ultomiris (ravulizumab-cwvz), which incorporates Xencor’s Xtend Fc Domain, was approved in the United States as the first and only long-acting C5 complement inhibitor for the treatment of adult patients with anti-aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum disorder (NMOSD). Ultomiris is also approved for certain adults with NMOSD in Japan and the European Union (EU). As part of Xencor’s recent Ultomiris royalty monetization, the Company remains eligible for certain future royalties and milestone payments. Ultomiris is a registered trademark of Alexion Pharmaceuticals, Inc.

•Single Dose of Investigational Antibody with Xtend Confers Protection Against Malaria Infection: Results from a Phase 2 National Institutes of Health (NIH)-sponsored clinical trial published in the New England Journal of Medicine showed that a single dose of L9LS, an experimental monoclonal antibody that incorporates Xencor’s Xtend Fc Domain, was up to 77% effective in preventing malaria in children in Mali for six months, demonstrating the long duration of action that Xtend technology can provide.

•New Chief Financial Officer Appointed: Bart Cornelissen was appointed as Xencor’s senior vice president and chief financial officer. He was most recently vice president, corporate finance at Seagen Inc.
Financial Guidance: Based on current operating plans, Xencor expects to end 2024 with between $475 million and $525 million in cash, cash equivalents and marketable debt securities, and to have cash to fund research and development programs and operations into 2027.
Financial Results for the First Quarter Ended March 31, 2024
Cash, cash equivalents and marketable debt securities totaled $646.7 million as of March 31, 2024, compared to $697.4 million on December 31, 2023.
Revenues for the first quarter ended March 31, 2024 were $12.8 million, compared to $19.0 million for the same period in 2023. Total revenues earned in the first quarter of 2024 included non-cash royalty revenue from Xencor’s Alexion and Morphosys/Incyte agreements, compared to milestone revenue earned from the J&J collaboration and royalties from the Alexion agreement in the first quarter of 2023.
Research and development expenses for the first quarter ended March 31, 2024 were $56.9 million, compared to $65.6 million for the same period in 2023. Decreased research and development spending for the first quarter of 2024 compared to 2023 reflects changes in spending across multiple clinical-stage programs and wind-down costs on terminated programs.
General and administrative expenses for the first quarter ended March 31, 2024 were $13.8 million and were in line with $14.2 million for the same period in 2023.
Other expense, net, for the first quarter ended March 31, 2024 was $10.8 million, compared to $0.02 million for the same period in 2023. Increased other expense for the first quarter of 2024 compared to 2023 reflects impairment charge on equity investments, partially offset by interest income earned on investments and unrealized gain on equity investments.

Non-cash, stock-based compensation expense for the first quarter ended March 31, 2024 was $11.4 million, compared to $12.6 million for the same period in 2023.

Net loss for the first quarter ended March 31, 2024 was $68.0 million, or $(1.11) on a fully diluted per share basis, compared to $60.8 million, or $(1.02) on a fully diluted per share basis, for the same period in 2023.

The total shares outstanding were 61,634,685 as of March 31, 2024, compared to 60,381,600 as of March 31, 2023.
Upcoming Investor Conferences
Company management will participate at multiple upcoming investor conferences:
•RBC Capital Markets Global Healthcare Conference
Date: Tuesday, May 14, 2024
Presentation Time: 2:05 p.m. ET / 11:05 a.m. PT
Location: New York City
•BofA Securities Health Care Conference
Date: Wednesday, May 15, 2024
Presentation Time: 4:40 p.m. ET / 1:40 p.m. PT
Location: Las Vegas

Live webcasts of the presentations will be available under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com. Replays of the events will be available on the Xencor website for at least 30 days following the presentations.

On May 9, 2024 Biohaven Ltd. (NYSE: BHVN) (Biohaven or the Company), a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies to treat a broad range of rare and common diseases, reported financial results for the first quarter ended March 31, 2024, and provided a review of recent accomplishments and anticipated upcoming developments (Press release, Biohaven Pharmaceutical, MAY 9, 2024, View Source [SID1234643097]).

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!

Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven, commented, "We are excited about the clinical progress we are making across our entire portfolio and in particular, the recent initiation of the first-in-human study of BHV-1300 using our Molecular Degrader of Extracellular Protein (MoDE) technology. We were pleased to report preliminary safety and target engagement data showing degradation of IgG from the initial two low-dose cohorts of the ongoing BHV-1300 study. Thus far, BHV-1300 has also been well-tolerated with no significant adverse effects and no clinically significant lab abnormalities or ECG changes observed to date. We remain enthusiastic about the emerging profile of BHV-1300 and have multiple IND-enabling activities planned for several additional MoDEs directed at autoantibody-mediated disease targets over the next couple of years. MoDEs represent a transformative technology to modulate the immune system and specifically degrade extracellular targets known to cause disease. INDs from our MoDE platform planned for later this year include drug candidates that target autoantibodies against β-1AR for the potential treatment of dilated cardiomyopathy and galactose deficient IgA for IgA nephropathy."

Dr. Coric continued, "The Biohaven R&D team continues to make impressive progress across our broader pipeline, with enrollment having begun in our BHV-7000 epilepsy program. In addition, dosing is now complete in Phase 1 SAD and MAD cohorts of BHV-8000, our TYK2/JAK1 inhibitor, paving the way for multiple clinical trial initiations in 2024, such as Parkinson’s disease, Alzheimer’s disease and prevention of Amyloid-Related Imaging Abnormalities (ARIA) associated with amyloid lowering agents. Additionally, Phase 3 trials are underway in OCD (obsessive-compulsive disorder), and in SMA, with data anticipated in both studies later this year. Further, multiple Phase 2 and Phase 2/3 studies initiated in Q2 in MDD, Bipolar Disorder and Generalized Epilepsy, and Phase 2 studies are projected to start in the second half of the year in migraine and obesity. And finally, important updates are expected with our burgeoning antibody drug conjugate (ADC) platform, with our recent initiation of enrollment in the TROP2 Phase 1 study, multiple INDs and 5–7 new ADC targets projected in the next two years. We excitedly await a steady cascade of anticipated upcoming milestones and were pleased to complete a public offering to further advance our development plans and research efforts. We look forward to unveiling further updates across our clinical programs and future development plans at our annual R&D Day at the Yale Innovation Summit on May 29, 2024 in New Haven, CT."

First Quarter 2024 and Recent Business Highlights

Reported preliminary safety and IgG lowering data from ongoing SAD study with BHV-1300 – In April 2024, the Company provided preliminary safety and IgG lowering data from its ongoing SAD study of BHV-1300. In the study, 16 subjects completed two dosing cohorts to date. All cohorts have proceeded as initially planned without any cohort expansion or interruption.
To date, BHV-1300 has been safe and well-tolerated with no serious adverse events (SAEs) or moderate or severe adverse events (Aes) observed. Only mild Aes have been observed, which were deemed not to be related to BHV-1300 with most resolving spontaneously. No clinically significant laboratory abnormalities (including liver function tests and albumin) or electrocardiogram (ECG) changes have been observed to date.
Preliminary IgG lowering data is consistent with modeling based on non-clinical experience, with dose- and time-dependent IgG lowering observed even in initial low dose cohorts. Reductions were greater for IgG1, IgG2 and IgG4 subclasses compared to IgG3; BHV-1300 was designed to spare IgG3.
Based on initial findings, the Company plans to accelerate development across additional autoantibody-mediated targets.
Phase 2/3 program with BHV-7000 underway in epilepsy – Also initiated a Phase 2 study in MDD and Phase 2/3 studies in Bipolar Disorder and Generalized Epilepsy with BHV-7000.
Taldefgrobep alfa awarded "rare pediatric disease" designation – In April 2024, the Company announced that the Food and Drug Administration (FDA) granted "rare pediatric disease" designation for taldefgrobep alfa. The designation provides the potential for taldefgrobep to receive a PRV if ultimately approved for the indication of SMA.
Oral and poster presentations at AAN showcased breadth of development work across the platform – In April 2024, the Company delivered 8 oral presentations and 12 posters at the AAN Annual Meeting, showcasing development programs including Kv7 ion channel modulation, MoDEs, TRPM3 antagonism, TYK2/JAK1 inhibition, glutamate modulation, and myostatin inhibition.
AAN Abstract of Distinction awarded to BHV-2100, which demonstrated potent reversal of pain in preclinical models and favorable initial safety and pharmacokinetic data in Phase 1 studies, highlighting the potential for TRPM3 antagonism as a novel nonopioid target to treat pain and migraine.
Biohaven’s first-in-class Molecular Degrader of Extracellular Proteins (MoDE) technology targeting IgG removal, BHV-1300, was selected for an oral presentation at AAN highlighting its novel mechanism of action and the latest preclinical data demonstrating rapid, robust, and selective target removal.
Public offering – On April 22, 2024, the Company closed its previously announced underwritten public offering of 6,451,220 of its common shares, which included the full exercise of the underwriters’ option to purchase 841,463 additional shares, at the public offering price of $41.00 per share. The net proceeds raised in the offering, after deducting underwriting discounts and estimated expenses of the offering payable by the Company, were approximately $247.8 million. As of May 6, 2024, we had 88,291,909 common shares outstanding.
Expected Upcoming Milestones:

We believe Biohaven is well positioned to achieve significant, value-creating milestones in 2024 across numerous programs:

Selective Kv7 Activator:

Continue to advance Phase 2/3 programs in focal epilepsy, idiopathic generalized epilepsy, MDD and bipolar disorder
Troriluzole:

Continue two Phase 3 trials with troriluzole in OCD
Taldefgrobep alfa:

Initiate taldefgrobep Phase 2 study in obesity in 2H 2024
Report taldefgrobep Phase 3 topline results in SMA in 2H 2024
First-in-class TRPM3 Antagonist:

Initiate BHV-2100 Phase 2 study in acute migraine in 2H 2024
Conduct BHV-2100 proof of concept (POC) study for neuropathic pain in 2H 2024
TYK2/JAK1 Inhibitor:

Complete SAD/MAD studies with BHV-8000 and advance to Phase 2 in 2H 2024
Extracellular protein degradation platform

A total of 4 Investigational New Drug Applications (INDs) are expected for the degrader program in 2024
Provide progress updates regarding ongoing Phase 1 SAD study with BHV-1300 at annual R&D Day on May 29, 2024 followed up with a MAD update in 2H24
Next Generation ADC Platform:

Advance Phase 1 TROP2 directed ADC program with BHV-1510 in multiple tumor types
Capital Position:

Cash, cash equivalents, marketable securities and restricted cash totaled approximately $287.6 million on March 31, 2024, which excludes the net proceeds of approximately $247.8 million from Biohaven’s public offering completed on April 22, 2024.

First Quarter 2024 Financial Highlights:

Research and Development (R&D) Expenses: R&D expenses, including non-cash share-based compensation costs, were $156.0 million for the three months ended March 31, 2024, compared to $63.5 million for the three months ended March 31, 2023. The increase of $92.5 million was primarily due to increases in direct program spend for additional and advancing clinical trials, including late Phase 2/3 studies, and preclinical research programs, as well as $16.6 million in common shares associated with the acquisition of Pyramid Biosciences, Inc., including a milestone payment for BHV-1510, and increased non-cash share-based compensation expense. Non-cash share-based compensation expense was $21.3 million for the three months ended March 31, 2024, an increase of $19.1 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in the first quarter of 2024 primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 and the first quarter of 2024.

General and Administrative (G&A) Expenses: General and administrative expenses were $27.3 million for the three months ended March 31, 2024, compared to $14.3 million for the three months ended March 31, 2023. The increase of $12.9 million was primarily due to increased non-cash share-based compensation expense. Non-cash share-based compensation expense was $13.6 million for the three months ended March 31, 2024, an increase of $12.1 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in the first quarter of 2024 primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 and the first quarter of 2024.

Other Income, Net: Other income, net was a net income of $4.3 million for the three months ended March 31, 2024, compared to a net income of $8.2 million for the three months ended March 31, 2023. The decrease of $3.9 million was primarily due to a decrease of $3.9 million in other income recognized during the three months ended March 31, 2024 as compared to the same period in 2023 related to the Transition Services Agreement entered into with Biohaven Pharmaceutical Holding Company Ltd. (the Former Parent).

Net Loss: Biohaven reported a net loss for the three months ended March 31, 2024, of $179.5 million, or $2.20 per share, compared to $70.5 million, or $1.03 per share, for the same period in 2023. Non-GAAP adjusted net loss for the three months ended March 31, 2024 was $144.6 million, or $1.77 per share, compared to $66.7 million, or $0.98 per share for the same period in 2023. These non-GAAP adjusted net loss and non-GAAP adjusted net loss per share measures, more fully described below under "Non-GAAP Financial Measures," exclude non-cash share-based compensation charges. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the tables below.

On May 9, 2024 Takeda reported that Quarterly Financial Report For the Quarter Ended March 31, 2024 (Presentation, Takeda, MAY 9, 2024, View Source [SID1234644742]).

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 May 9, 2024 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported that management will participate in the following upcoming investor conferences (Press release, Alector, MAY 9, 2024, View Source [SID1234642973]):

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!

Bank of America Securities Health Care Conference (Las Vegas, Nevada)
Tuesday, May 14, 2024, at 8:55 a.m. PT, corporate presentation
H.C. Wainwright 2nd Annual BioConnect Investor Conference (New York, New York)
Monday, May 20, 2024, at 11:00 a.m. ET, fireside chat
A webcast of each conference presentation will be available on the "Events & Presentations" page within the Investors section of the Alector website at View Source Replays of the webcasts will be available on the Alector website for 90 days following the presentation dates.