On October 31, 2024 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage T-cell reprogramming company advancing a pipeline of next-generation CAR T-cell therapies for patients with solid tumors or hematologic malignancies, reported that it has completed its acquisition of ImmPACT Bio USA Inc. ("ImmPACT"), a privately-owned clinical-stage cell therapy company (Press release, Lyell Immunopharma, OCT 31, 2024, View Source [SID1234647604]). The acquisition strengthens Lyell’s clinical-stage pipeline of CAR T-cell therapies and complements its suite of innovative technologies designed to generate longer-lasting, functional T cells to achieve more durable outcomes for patients. Lyell will accelerate the development of IMPT-314, a dual-targeting CD19/20 chimeric antigen receptor (CAR) T-cell product candidate for hematologic malignancies, including B-cell non-Hodgkin lymphoma. In connection with the acquisition, Sumant Ramachandra, M.D., Ph.D., MBA, the former Chief Executive Officer of ImmPACT Bio, has been appointed to the Lyell Board of Directors.

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"We’re excited to welcome ImmPACT to Lyell and look forward to working together to transform the treatment of cancer with next-generation cell therapies that offer patients improved outcomes," stated Lynn Seely, M.D., Lyell’s President and Chief Executive Officer. "We are focused on accelerating the development of IMPT-314 for patients with aggressive B-cell non-Hodgkin lymphoma and look forward to presenting initial data from the Phase 1-2 trial of IMPT-314 in patients treated in the 3rd line CAR-naïve setting at a major medical conference later this year."

"On behalf of my fellow directors, I am delighted to welcome Dr. Ramachandra to the Lyell Board," stated Rick Klausner, M.D., chair of Lyell’s Board of Directors. "Dr. Ramachandra’s experience and passion for developing innovative therapies for patients will help guide us as we integrate our two organizations and advance a pipeline of next-generation CAR T-cell therapies."

Dr. Ramachandra has served as the Chief Executive Officer of ImmPACT Bio USA, Inc. since November 2021. He also served as a member of the board of directors of ImmPACT from December 2021 to October 2024. Prior to joining ImmPACT, Dr. Ramachandra was most recently Chief Science, Technology and Medical Officer of Baxter International. In addition to these responsibilities, he was appointed President of Baxter Pharmaceuticals. Prior to Baxter, he worked at Pfizer, most recently as Senior Vice President, Head of Research & Development, Pfizer Essential Health. He served as Chief Scientific Officer at Hospira from 2008 to 2015 prior to Pfizer’s acquisition of Hospira in 2015. Before entering the industry in 2000, he was an intern and resident physician, medical services, at Massachusetts General Hospital, Harvard Medical School. Dr. Ramachandra completed his undergraduate degree in biochemistry, graduate degree (Ph.D.) in experimental pathology in the study of chronic lymphocytic leukemia and his medical degree (M.D.) at Rutgers University. In addition, he earned his M.B.A. at The Wharton School at the University of Pennsylvania.

As previously disclosed, following the closing of this acquisition, Lyell expects its cash balance will fund operations into 2027, through important clinical milestones for each pipeline program, including initiation of a pivotal trial for IMPT-314, which is expected to start in 2025.

On October 31, 2024 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company") reported that the new drug application (NDA) (the "Application") based on the positive results from the pivotal phase III OptiTROP-Lung04 study of sacituzumab tirumotecan (sac-TMT, that it formerly SKB264/MK-2870) developed was accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China in adult patients with epidermal growth factor receptor (EGFR)-mutant locally advanced or metastatic non-small cell lung cancer (NSCLC) who progressed after treatment with EGFR-tyrosine kinase inhibitor (TKI) therapy (Press release, Kelun, OCT 31, 2024, View Source [SID1234647620]).

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OptiTROP-Lung04 is a multi-center, randomized, registrational phase III clinical study that evaluates the efficacy and safety results of sac-TMT monotherapy versus pemetrexed plus platinum chemotherapy for the treatment of patients with EGFR-mutant locally advanced or metastatic NSCLC who progressed after treatment with EGFR- TKI therapy. At a pre-specified interim analysis, sac-TMT monotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS) as assessed by the blinded independent review committee (BIRC) compared with pemetrexed plus platinum chemotherapy. Sac-TMT also showed a manageable safety profile, with no unexpected safety signals identified.

The Application is the third NDA for sac-TMT that has been accepted by the NMPA. On October 25, 2024, it was announced on the official website of the CDE that the Application was planned to be included in the priority review and approval process of the CDE.

Previously, two NDAs for sac-TMT in patients with locally advanced or metastatic triple-negative breast cancer (TNBC) who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting) and for sac-TMT monotherapy in adult patients with locally advanced or metastatic EGFR-mutant NSCLC who experience progression following treatment with an EGFR-TKI and platinum-based chemotherapy, respectively, were accepted by the NMPA.

Sac-TMT, a core product of the Company, is a novel human trophoblast cell-surface antigen 2 (TROP2) antibody-drug conjugate (ADC) in which the Company has proprietary intellectual property rights, targeting advanced solid tumors such as NSCLC, breast cancer (BC), gastric cancer (GC), gynecological tumors, among others. Sac-TMT is developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor with a drug-to-antibody-ratio (DAR) of 7.4. Sac-TMT specifically recognizes TROP2 on the surface of tumor cells by recombinant anti-TROP2 humanized monoclonal antibodies, which is then endocytosed by tumor cells and releases KL610023 intracellularly. KL610023, as a topoisomerase I inhibitor, induces DNA damage to tumor cells, which in turn leads to cell-cycle arrest and apoptosis. In addition, it also releases KL610023 in the tumor microenvironment. Given that KL610023 is membrane permeable, it can enable a bystander effect, or in other words kill adjacent tumor cells.

In May 2022, the Company licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc., Rahway, NJ, USA) to develop, use, manufacture and commercialize sac-TMT in all territories outside of Greater China (includes Mainland China, Hong Kong, Macao, and Taiwan).

Dr. Micheal Ge, CEO of Kelun-Biotech, said, "sac-TMT (sacituzumab govitecan) has received its third NDA. In response to unmet clinical needs, the company has always adhered to the spirit of hard work inherent in Kelun, focusing on original innovation and doing practical work to develop new drugs with differentiated advantages and international potential. We believe that sac-TMT will shine in the field of oncology and contribute Chinese strength to the global health cause."

On October 31, 2024 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported financial results for the third quarter of 2024 (Press release, Merck & Co, OCT 31, 2024, View Source [SID1234647605]).

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"Our third-quarter results were strong, as we continue to make progress heading into 2025 and beyond," said Robert M. Davis, chairman and chief executive officer, Merck. "Our pipeline is advancing and expanding, demonstrating our success in creating a sustainable innovation engine, and positioning Merck with a more diversified portfolio to drive growth. I continue to remain confident in the strength of our business and our ability to execute, and I want to thank our colleagues across the globe for their focus and commitment as we work to create lasting value for patients, shareholders and all our stakeholders."

Financial Summary

$ in millions, except EPS amounts

Third Quarter

2024

2023

Change

Change Ex-
Exchange

Sales

$16,657

$15,962

4%

7%

GAAP net income1

3,157

4,745

-33%

-30%

Non-GAAP net income that excludes certain items1,2*

3,985

5,427

-27%

-23%

GAAP EPS

1.24

1.86

-33%

-30%

Non-GAAP EPS that excludes certain items2*

1.57

2.13

-26%

-23%

*Refer to table on page 7.

In the third quarter of 2024, total worldwide sales were $16.7 billion, an increase of 4% compared with the third quarter of 2023; excluding the impact of foreign exchange, growth was 7%. Sales growth in the third quarter of 2024 was primarily due to increased usage of KEYTRUDA globally, contributions from new launches, including WINREVAIR and CAPVAXIVE, and strong growth in Merck’s Animal Health business. Revenue growth in the third quarter of 2024 was partially offset by lower sales of JANUVIA and JANUMET, lower combined sales of GARDASIL/GARDASIL 9 and lower sales of LAGEVRIO. Third-quarter GARDASIL/GARDASIL 9 sales declined year-over-year due to reduced demand in China; outside of China, the company achieved double-digit sales growth for GARDASIL/GARDASIL 9 in almost every major region globally.

For the third quarter of 2024, Generally Accepted Accounting Principles (GAAP) earnings per share (EPS) assuming dilution was $1.24 and non-GAAP EPS was $1.57. The declines in GAAP and Non-GAAP EPS in the third quarter of 2024 versus the prior year were largely due to a net charge of $0.79 per share in the aggregate for the acquisition of Eyebiotech Limited (EyeBio) and a related development milestone, the acquisition of CN201 (now known as MK-1045) from Curon Biopharmaceutical (Curon), as well as a payment received from Daiichi Sankyo related to the expansion of the existing development and commercialization agreement. There were no significant business development transaction charges in the third quarter of 2023.

Non-GAAP EPS in both periods excludes acquisition- and divestiture-related costs, costs related to restructuring programs, as well as income and losses from investments in equity securities.

Year-to-date results can be found in the attached tables.

Third-Quarter Sales Performance

The following table reflects sales of the company’s top products and significant performance drivers.

Third Quarter

$ in millions

2024

2023

Change

Change
Ex-
Exchange

Commentary

Total Sales

$16,657

$15,962

4%

7%

Approximately 2 percentage points of the negative impact of foreign exchange was due to devaluation of Argentine peso, which was largely offset by inflation-related price increases, consistent with practice in that market.

Pharmaceutical

14,943

14,263

5%

8%

Increase driven by growth in oncology and cardiovascular, partially offset by declines in diabetes, vaccines and virology.

KEYTRUDA

7,429

6,338

17%

21%

Growth driven by increased global uptake in earlier-stage indications, including triple-negative breast cancer (TNBC), renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC), as well as continued strong global demand from metastatic indications. Approximately 3 percentage points of the negative impact of foreign exchange was due to devaluation of Argentine peso, which was largely offset by inflation-related price increases.

GARDASIL/GARDASIL 9

2,306

2,585

-11%

-10%

Decline primarily due to lower demand in China compared with prior year, partially offset by higher sales in the U.S., driven by public-sector buying patterns, higher pricing and demand, as well as higher demand in most international regions.

PROQUAD, M-M-R II and VARIVAX

703

713

-1%

-1%

Decline primarily due to timing of shipments and lower tenders in Latin America, largely offset by higher demand in certain international markets.

JANUVIA/JANUMET

482

835

-42%

-38%

Decline primarily due to lower pricing in the U.S., as well as ongoing generic competition in many international markets.

BRIDION

420

424

-1%

0%

Relatively flat compared with prior year due to generic competition in certain international markets, particularly in Europe and Japan, largely offset by higher demand and pricing in the U.S.

LAGEVRIO

383

640

-40%

-36%

Decline primarily due to lower demand in Japan, partially offset by uptake from commercial launch in the U.S.

Lynparza*

337

299

13%

13%

Growth primarily due to higher global demand.

Lenvima*

251

260

-3%

-4%

Decline primarily due to timing of shipments in China in the prior year, partially offset by higher demand in the U.S.

VAXNEUVANCE

239

214

12%

13%

Growth largely driven by continued uptake from launches in Europe and Japan, partially offset by lower demand in the U.S. due to competition.

PREVYMIS

208

157

32%

36%

Growth primarily due to higher global demand, particularly in the U.S.

ROTATEQ

193

156

24%

25%

Growth primarily due to public-sector buying patterns in the U.S. and timing of shipments in China.

WINREVAIR

149

–

–

–

Represents continued uptake since launch in the U.S. in the second quarter.

WELIREG

139

54

156%

157%

Growth primarily driven by higher demand in the U.S., largely attributable to ongoing uptake of a new indication.

Animal Health

1,487

1,400

6%

11%

Growth primarily driven by higher demand and pricing for both Companion Animal and Livestock product portfolios, as well as sales related to July 2024 acquisition of Elanco aqua business. Approximately 2 percentage points of the negative impact of foreign exchange was due to devaluation of Argentine peso, which was largely offset by inflation-related price increases.

Livestock

886

874

1%

7%

Growth primarily driven by higher pricing and higher demand for poultry and swine products, as well as sales related to acquisition of Elanco aqua business.

Companion Animal

601

526

14%

17%

Growth primarily driven by uptake from new product launches, including the injectable formulation of BRAVECTO in certain international markets, as well as higher pricing across product portfolio. Sales of BRAVECTO were $266 million and $235 million in current and prior year quarters, respectively, which represented growth of 13%, or 16% excluding impact of foreign exchange.

Other Revenues**

227

299

-24%

-22%

Decline primarily due to lower payments received for out-licensing arrangements and lower royalty income.

*Alliance revenue for this product represents Merck’s share of profits, which are product sales net of cost of sales and commercialization costs.
**Other revenues are comprised primarily of revenues from third-party manufacturing arrangements and miscellaneous corporate revenues, including revenue-hedging activities.

Third-Quarter Expense, EPS and Related Information

The table below presents selected expense information.

$ in millions

GAAP

Acquisition-
and
Divestiture-
Related
Costs3

Restructuring
Costs

(Income)
Loss From
Investments
in Equity
Securities

Non-
GAAP2

Third Quarter 2024

Cost of sales

$4,080

$639

$192

$-

$3,249

Selling, general and administrative

2,731

43

31

–

2,657

Research and development

5,862

24

–

–

5,838

Restructuring costs

56

–

56

–

–

Other (income) expense, net

(162)

(27)

–

58

(193)

Third Quarter 2023

Cost of sales

$4,264

$552

$33

$-

$3,679

Selling, general and administrative

2,519

17

40

–

2,462

Research and development

3,307

10

–

–

3,297

Restructuring costs

126

–

126

–

–

Other (income) expense, net

126

(24)

–

17

133

GAAP Expense, EPS and Related Information

Gross margin was 75.5% for the third quarter of 2024 compared with 73.3% for the third quarter of 2023. The increase was primarily due to the favorable impact of product mix (including lower royalty rates related to KEYTRUDA and GARDASIL/GARDASIL 9), partially offset by higher restructuring costs (primarily reflecting asset impairment charges), as well as higher amortization of intangible assets.

Selling, general and administrative (SG&A) expenses were $2.7 billion in the third quarter of 2024, an increase of 8% compared with the third quarter of 2023. The increase was primarily due to higher administrative, promotional, selling, and acquisition-related costs, partially offset by the favorable impact of foreign exchange.

Research and development (R&D) expenses were $5.9 billion in the third quarter of 2024, an increase of 77% compared with the third quarter of 2023. The increase was primarily due to a charge of $1.35 billion for the acquisition of EyeBio and a $100 million charge for a related development milestone, as well as a charge of $750 million to acquire CN201 (MK-1045) from Curon. The increase in R&D expenses was also driven by higher compensation and benefit costs, as well as higher clinical development spending. The increase in R&D expenses was partially offset by the favorable impact of foreign exchange.

Other (income) expense, net, was $162 million of income in the third quarter of 2024 compared with $126 million of expense in the third quarter of 2023. The favorability was primarily due to a $170 million payment received from Daiichi Sankyo related to the expansion of the existing development and commercialization agreement, lower exchange losses and lower net interest expense.

The effective tax rate of 22.7% for the third quarter of 2024 includes a 7.2 percentage point combined unfavorable impact related to the EyeBio and Curon transactions.

GAAP EPS was $1.24 for the third quarter of 2024 compared with $1.86 for the third quarter of 2023. GAAP EPS in the third quarter of 2024 includes a net charge of $0.79 per share in the aggregate for the EyeBio, Curon and Daiichi Sankyo transactions. There were no significant business development transaction charges in the third quarter of 2023.

Non-GAAP Expense, EPS and Related Information

Non-GAAP gross margin was 80.5% for the third quarter of 2024 compared with 77.0% for the third quarter of 2023. The increase was primarily due to the favorable impact of product mix (including lower royalty rates related to KEYTRUDA and GARDASIL/GARDASIL 9).

Non-GAAP SG&A expenses were $2.7 billion in the third quarter of 2024, an increase of 8% compared with the third quarter of 2023. The increase was primarily due to higher administrative, promotional and selling costs, partially offset by the favorable impact of foreign exchange.

Non-GAAP R&D expenses were $5.8 billion in the third quarter of 2024, an increase of 77% compared with the third quarter of 2023. The increase was primarily due to a charge of $1.35 billion for the acquisition of EyeBio and a $100 million charge for a related development milestone, as well as a charge of $750 million to acquire CN201 (MK-1045) from Curon. The increase in R&D expenses was also driven by higher compensation and benefit costs, as well as higher clinical development spending. The increase in R&D expenses was partially offset by the favorable impact of foreign exchange.

Non-GAAP other (income) expense, net, was $193 million of income in the third quarter of 2024 compared with $133 million of expense in the third quarter of 2023. The favorability was primarily due to a $170 million payment received from Daiichi Sankyo related to the expansion of the existing development and commercialization agreement, lower exchange losses and lower net interest expense.

The non-GAAP effective tax rate of 21.9% for the third quarter of 2024 includes a 6.0 percentage point combined unfavorable impact related to the EyeBio and Curon transactions.

Non-GAAP EPS was $1.57 for the third quarter of 2024 compared with $2.13 for the third quarter of 2023. Non-GAAP EPS in the third quarter of 2024 includes a net charge of $0.79 per share in the aggregate for the EyeBio, Curon and Daiichi Sankyo transactions. There were no significant business development transaction charges in the third quarter of 2023.

A reconciliation of GAAP to non-GAAP net income and EPS is provided in the table that follows.

Third Quarter

$ in millions, except EPS amounts

2024

2023

EPS

GAAP EPS

$1.24

$1.86

Difference

0.33

0.27

Non-GAAP EPS that excludes items listed below2

$1.57

$2.13

Net Income

GAAP net income1

$3,157

$4,745

Difference

828

682

Non-GAAP net income that excludes items listed below1,2

$3,985

$5,427

Excluded Items:

Acquisition- and divestiture-related costs3

$679

$555

Restructuring costs

279

199

Loss from investments in equity securities

58

17

Decrease to net income

1,016

771

Estimated income tax (benefit) expense

(188)

(89)

Decrease to net income

$828

$682

Pipeline and Portfolio Highlights

In the third quarter, Merck continued to develop and augment its strong, diverse pipeline and achieve key regulatory and clinical milestones.

In cardiovascular disease, Merck continued to build on positive momentum in its U.S. launch of WINREVAIR. As of the end of September 2024, more than 3,700 patients have been prescribed WINREVAIR. The company also received the European Commission’s (EC) approval of WINREVAIR, in combination with other pulmonary arterial hypertension (PAH) therapies, for the treatment of adult patients with PAH with World Health Organization (WHO) functional Class II to III. WINREVAIR is the first activin signaling inhibitor approved for the treatment of PAH in Europe. WINREVAIR has launched in Germany and Merck is working to obtain reimbursement for WINREVAIR in other countries in the EU, which should occur in most other major European markets in the second half of 2025.

In oncology, Merck continued to reinforce its leadership in women’s and earlier stages of cancers and demonstrate progress in its research pipeline. At the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024, three of the company’s data presentations were highlighted during Presidential Symposium sessions. These included overall survival (OS) data from the Phase 3 KEYNOTE-522 trial in high-risk, early-stage TNBC and from the Phase 3 KEYNOTE-A18 trial (also known as ENGOT-cx11/GOG-3047) in high-risk, locally advanced cervical cancer. In addition, new positive data on investigational candidates from Merck’s pipeline were presented, including for patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate (ADC) being developed in collaboration with Daiichi Sankyo, and for sacituzumab tirumotecan (sac-TMT), an anti-TROP2 ADC being developed in collaboration with Kelun-Biotech.

The company also achieved several regulatory milestones, including new approvals for KEYTRUDA-based regimens in the U.S., Europe and Japan. In addition, Merck recently announced top-line results from the KEYNOTE-689 trial, which marks the first positive trial in two decades for patients with resected, locally advanced head and neck squamous cell carcinoma (LA-HNSCC).

In vaccines, the CDC’s Advisory Committee on Immunization Practices (ACIP) voted in October 2024 to recommend CAPVAXIVE for individuals 50 to 64 years of age. This decision expanded upon the initial unanimous recommendation in June 2024 for use of CAPVAXIVE in adults age 65 and older, among other cohorts.

At IDWeek 2024, Merck presented positive results from the Phase 2b/3 trial of clesrovimab (MK-1654), an investigational respiratory syncytial virus (RSV) preventative monoclonal antibody for infants. These results support the potential for clesrovimab to become the first and only single-dose immunization designed to protect infants with the same dose, regardless of weight, for the duration of their first RSV season (six months).

In immunology, long-term efficacy and safety data for tulisokibart (MK-7240), an investigational humanized monoclonal antibody directed to a novel target, tumor necrosis factor (TNF)-like cytokine 1A (TL1A), from the Phase 2 ARTEMIS-UC and APOLLO-CD studies in ulcerative colitis (UC) and Crohn’s disease (CD), were presented at the United European Gastroenterology (UEG) Week 2024 Congress. Both studies showed that, at week 50, maintenance of treatment efficacy was generally observed in 12-week induction responders. Phase 3 studies in UC and CD are ongoing.

In addition, Merck continued to expand and diversify its pipeline by securing strategic business development opportunities. Merck completed its acquisition of CN201 (MK-1045), a next-generation CD3xCD19 bispecific antibody with potential applications in B-cell malignancies and autoimmune diseases, from Curon. Merck also announced the expansion of the global development and commercialization agreement with Daiichi Sankyo to include MK-6070, an investigational delta-like ligand 3 (DLL3) targeting T-cell engager. The companies are planning to evaluate MK-6070 in combination with ifinatamab deruxtecan (I-DXd) in certain patients with small cell lung cancer (SCLC), as well as other potential combinations.

Notable recent news releases on Merck’s pipeline and portfolio are provided in the table that follows.

Oncology

FDA Approved KEYTRUDA Plus Pemetrexed and Platinum Chemotherapy as First-Line Treatment for Adult Patients With Unresectable Advanced or Metastatic Malignant Pleural Mesothelioma, Based on Results From Phase 3 KEYNOTE-483/CCTG IND.227 Trial

(Read Announcement)

EC Approved KEYTRUDA Plus Padcev as First-Line Treatment of Unresectable or Metastatic Urothelial Carcinoma in Adults, Based on Results From Phase 3 KEYNOTE-A39/EV-302 Trial

(Read Announcement)

KEYTRUDA Received 30th Approval From EC With Two New Indications in Gynecologic Cancers, Based on Results From Phase 3 KEYNOTE-868/NRG-GY018 and KEYNOTE-A18 Trials

(Read Announcement)

KEYTRUDA Received New Approvals in Japan for Certain Patients With NSCLC, Based on Results From Phase 3 KEYNOTE-671 Trial, and for Radically Unresectable Urothelial Carcinoma, Based on Results From Phase 3 KEYNOTE-A39/EV-302 and Phase 2 KEYNOTE-052 Trials

(Read Announcement)

KEYTRUDA Plus Chemotherapy Before Surgery and Continued as Single Agent After Surgery Reduced Risk of Death by More Than One-Third (34%) Versus Neoadjuvant Chemotherapy in High-Risk, Early-Stage TNBC, Based on Results From Phase 3 KEYNOTE-522

(Read Announcement)

KEYTRUDA Plus Chemoradiotherapy (CRT) Reduced Risk of Death by 33% Versus CRT Alone in Patients With Newly Diagnosed, High-Risk, Locally Advanced Cervical Cancer, Based on Results From Phase 3 KEYNOTE-A18/ENGOT-cx11/GOG-3047 Trial

(Read Announcement)

KEYTRUDA Ten-Year Data Demonstrated Sustained OS Benefit Versus Ipilimumab in Advanced Melanoma, Based on Results From Phase 3 KEYNOTE-006 Trial

(Read Announcement)

KEYTRUDA Plus Lenvima in Combination With Transarterial Chemoembolization (TACE) Significantly Improved Progression-Free Survival Compared to TACE Alone in Patients With Unresectable, Non-Metastatic Hepatocellular Carcinoma, Based on Results From Phase 3 LEAP-012 Trial

(Read Announcement)

KEYTRUDA Plus Trastuzumab and Chemotherapy Significantly Improved OS Versus Trastuzumab and Chemotherapy Alone in First-Line Treatment of Patients With HER2-Positive Advanced Gastric or GEJ Adenocarcinoma, Based on Results From Phase 3 KEYNOTE-811 Trial

(Read Announcement)

KEYTRUDA Met Primary Endpoint of Event-Free Survival as Perioperative Treatment Regimen in Patients With Resected, LA-HNSCC, Based on Results From Phase 3 KEYNOTE-689 Trial

(Read Announcement)

Patritumab Deruxtecan (HER3-DXd) Demonstrated Statistically Significant Improvement in Progression-Free Survival Versus Doublet Chemotherapy in Patients With Locally Advanced or Metastatic EGFR-Mutated NSCLC, Based on Results From Phase 3 HERTHENA-Lung02 Trial

(Read Announcement)

Ifinatamab Deruxtecan Continued to Demonstrate Promising Objective Response Rates in Patients With Extensive-Stage SCLC, Based on Results From Phase 2 IDeate-Lung01 Trial

(Read Announcement)

Merck and Moderna Initiated Phase 3 Trial Evaluating Adjuvant V940 (mRNA-4157) in Combination With KEYTRUDA After Neoadjuvant KEYTRUDA and Chemotherapy in Patients With Certain Types of NSCLC

(Read Announcement)

Merck Initiated Phase 3 Shorespan-007 Trial for Bomedemstat, an Investigational Candidate for the Treatment of Certain Patients With Essential Thrombocythemia

(Read Announcement)

Merck and Daiichi Sankyo Initiated Phase 3 IDeate-Lung02 Trial of Ifinatamab Deruxtecan in Patients With Relapsed SCLC

(Read Announcement)

Merck and Exelixis Signed Clinical Development Collaboration To Evaluate Investigational Zanzalintinib in Combination With KEYTRUDA in Head and Neck Cancer and in Combination With WELIREG in RCC

(Read Announcement)

Vaccines

Clesrovimab (MK-1654), an Investigational RSV Preventative Monoclonal Antibody, Significantly Reduced Incidence of RSV Disease and Hospitalization in Healthy Preterm and Full-Term Infants, Based on Results From Phase 2b/3 MK-1654-004 Trial

(Read Announcement)

CDC’s ACIP Recommended CAPVAXIVE for Pneumococcal Vaccination in Adults 50 Years of Age and Older

(Read Announcement)

CAPVAXIVE Demonstrated Positive Immune Responses in Adults With Increased Risk for Pneumococcal Disease, Based on Results From Phase 3 STRIDE-8 Trial

(Read Announcement)

Merck Announced Positive Top-line Results From Phase 3 Trial Evaluating Efficacy and Safety of GARDASIL 9 in Japanese Males

(Read Announcement)

Cardiovascular

EC Approved WINREVAIR in Combination With Other PAH Therapies for the Treatment of PAH in Adult Patients With Functional Class II-III, Based on Results From Phase 3 STELLAR Trial

(Read Announcement)

Immunology

Merck Presented New Long-Term Data for Tulisokibart (MK-7240), an Investigational Anti-TL1A Monoclonal Antibody, in Inflammatory Bowel Disease at UEG Week 2024

(Read Announcement)

Infectious Diseases

Merck and Gilead Announced Phase 2 Data Showing a Treatment Switch to an Investigational Oral Once-Weekly Combination Regimen of Islatravir and Lenacapavir (MK-8591D) Maintained Viral Suppression in Adults at Week 48

(Read Announcement)

Ophthalmology

Merck and EyeBio Initiated Phase 2b/3 Clinical Trial for MK-3000 for the Treatment of Diabetic Macular Edema

(Read Announcement)

Sustainability Highlights

Merck issued its 2023/2024 Impact Report, reaffirming its commitment to operating responsibly and enabling broad access to its products. The report noted how the company reached more than 550 million people around the world with its medicines and vaccines through commercial channels, clinical trials, voluntary licensing and product donations.

Full-Year 2024 Financial Outlook

The following table summarizes the company’s full-year financial outlook.

Full Year 2024

Updated

Prior

Sales*

$63.6 to $64.1 billion

$63.4 to $64.4 billion

Non-GAAP Gross margin2

Approximately 81%

Approximately 81%

Non-GAAP Operating expenses2**

$27.8 to $28.3 billion

$26.8 to $27.6 billion

Non-GAAP Other (income) expense, net2

Approximately $100 million expense

Approximately $350 million expense

Non-GAAP Effective tax rate2

16.0% to 17.0%

15.5% to 16.5%

Non-GAAP EPS2***

$7.72 to $7.77

$7.94 to $8.04

Share count (assuming dilution)

Approximately 2.54 billion

Approximately 2.54 billion

*The company does not have any non-GAAP adjustments to sales.

**Includes one-time R&D charges of $656 million for Harpoon Therapeutics, Inc. (Harpoon) acquisition, $1.45 billion for EyeBio acquisition and related development milestone payment, and $750 million for acquisition of CN201 (MK-1045) from Curon. Outlook does not assume any additional significant potential business development transactions.

***Includes net one-time charge of $1.05 per share in aggregate for the Harpoon, EyeBio and Curon transactions, and the cash payment received from Daiichi Sankyo.

Merck has not provided a reconciliation of forward-looking non-GAAP gross margin, non-GAAP operating expenses, non-GAAP other (income) expense, net, non-GAAP effective tax rate and non-GAAP EPS to the most directly comparable GAAP measures, given it cannot predict with reasonable certainty the amounts necessary for such a reconciliation, including intangible asset impairment charges, legal settlements, and gains and losses from investments in equity securities either owned directly or through ownership interests in investment funds, without unreasonable effort. These items are inherently difficult to forecast and could have a significant impact on the company’s future GAAP results.

Merck continues to experience strong growth, including from KEYTRUDA, new product launches and Animal Health. As a result, Merck is narrowing the range of its full-year sales outlook.

Merck now expects its full-year sales to be between $63.6 billion and $64.1 billion, including a negative impact of foreign exchange of approximately 3 percentage points, at mid-October 2024 exchange rates. Approximately 2 percentage points of the negative impact of foreign exchange is due to the devaluation of the Argentine peso, which is being largely offset by inflation-related price increases, consistent with practice in that market.

Merck now expects its full-year non-GAAP effective income tax rate to be between 16.0% and 17.0%, which includes an unfavorable impact related to the one-time charge associated with the acquisition of CN201 (MK-1045) from Curon.

Merck now expects its full-year non-GAAP EPS to be between $7.72 and $7.77. The outlook includes a negative impact of foreign exchange of approximately $0.30 per share. The negative impact of foreign exchange is primarily due to the devaluation of the Argentine peso, which is being largely offset by inflation-related price increases, consistent with practice in that market. This revised non-GAAP EPS range reflects a net charge of $0.24 per share for the following items not previously included in the outlook:

The acquisition of CN201 (MK-1045) from Curon.
Payment received from Daiichi Sankyo related to the expansion of the existing development and commercialization agreement.
Consistent with past practice, the financial outlook does not assume additional significant potential business development transactions.

Non-GAAP EPS excludes acquisition- and divestiture-related costs, costs related to restructuring programs, income and losses from investments in equity securities, as well as a tax benefit in 2024 due to a reduction in reserves for unrecognized income tax benefits, resulting from the expiration of the statute of limitations for assessments related to the 2019 federal tax return year.

Earnings Conference Call

Investors, journalists and the general public may access a live audio webcast of the earnings conference call on Thursday, October 31, at 9 a.m. ET via this weblink. A replay of the webcast, along with the sales and earnings news release, supplemental financial disclosures, and slides highlighting the results, will be available at www.merck.com.

All participants may join the call by dialing (800) 369-3351 (U.S. and Canada Toll-Free) or (517) 308-9448 and using the access code 9818590.

On October 31, 2024 Vir Biotechnology, Inc. (Nasdaq: VIR) reported a corporate update and announced financial results for the third quarter ended September 30, 2024 (Press release, Vir Biotechnology, OCT 31, 2024, View Source [SID1234647621]).

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"This quarter was transformational for Vir. We have bolstered our clinical pipeline with three potential best-in-class dual-masked T-cell engagers in oncology, and have sharpened our focus within infectious diseases to the areas where we believe we can make the most significant impact for patients. We are also thrilled to welcome Jason O’Byrne as our new CFO. Jason brings a wealth of financial leadership experience, further strengthening our ability to bring these potentially transformative therapies to patients as quickly as possible," said Marianne De Backer, M.Sc., Ph.D., MBA, Chief Executive Officer, Vir Biotechnology. "Looking ahead, this is an exciting time for the Company. We eagerly anticipate critical data in our hepatitis programs in the fourth quarter and look forward to sharing initial clinical data from our dual-masked T-cell engagers in the first quarter of 2025."

Pipeline Programs

Chronic Hepatitis Delta (CHD)

Preliminary data from the Phase 2 chronic hepatitis delta SOLSTICE study was presented at the European Study of the Liver (EASL) Meeting in June 2024. This data demonstrated the potential for transformative treatment for people living with chronic hepatitis delta, with both tobevibart as a monotherapy, and in combination with elebsiran, achieving high rates of virologic response and ALT normalization after 12 and 24 weeks of treatment. No treatment-related serious adverse events were observed.
The combination of tobevibart and elebsiran has been granted Fast Track Designation by the U.S. FDA. Given the robust rates of virologic suppression observed with the combination, the Company is diligently working to advance this regimen into a pivotal development program as quickly as possible to address the urgent needs of these patients.
At the upcoming American Association for the Study of Liver Diseases (AASLD) "The Liver Meeting" in November 2024, the Company will present additional data from the Phase 2 chronic hepatitis delta SOLSTICE trial, including: 24-week clinical data for both study cohorts in approximately 60 patients and further data for those patients who were on study beyond 24 weeks at the time of data cut-off.
One cohort assesses the combination of tobevibart and elebsiran administered every four weeks, while a second cohort evaluates tobevibart monotherapy administered every two weeks.
The SOLSTICE trial is evaluating the safety, tolerability and efficacy of tobevibart and elebsiran for the treatment of chronic hepatitis delta.
Chronic Hepatitis B (CHB)

The Company plans to share end-of-treatment data from the Phase 2 MARCH Part B trial as a Late Breaking presentation at the AASLD meeting in November 2024.
The MARCH-B trial is evaluating the safety, tolerability and antiviral activity of the triplet combination of tobevibart and elebsiran plus peginterferon alfa-2a in approximately 30 participants, and approximately 50 participants treated with the doublet combination of tobevibart and elebsiran.
The Company plans to share further data assessing a potential functional cure in the second quarter of 2025.
Solid Tumors

VIR-5818 is a dual-masked HER2-targeted T-cell engager in clinical development designed to minimize off-tumor toxicity, potentially allowing for higher doses and increased efficacy to address the significant unmet needs of patients with HER2 expressing cancers.
A Phase 1 basket study of VIR-5818 as a monotherapy, and in combination with pembrolizumab, is on-going in multiple tumor types, including metastatic breast cancer and metastatic colorectal cancer.
The Company plans to share initial clinical data for VIR-5818 in the first quarter of 2025.
VIR-5500 is a dual-masked PSMA directed T-cell engager in clinical development designed to minimize off-tumor toxicity and potentially improve efficacy relative to the existing approved PSMA-targeted therapies.
A Phase 1 dose escalation study of VIR-5500 is ongoing to assess its safety profile and optimal dose levels for future development in metastatic-castration resistant prostate cancer.
The Company plans to share initial clinical data for VIR-5500 in the first quarter of 2025.
VIR-5525 is a dual-masked EGFR targeted T-cell engager with a cleared Investigational New Drug Application (IND) from the U.S. FDA.
The Company plans to initiate a Phase 1 basket study of VIR-5525 in the first quarter of 2025 in patients across a number of solid tumor indications of high unmet need, which may include metastatic head and neck squamous cell carcinoma, metastatic adenocarcinoma, squamous non-small cell lung cancer, and metastatic colorectal cancer.
Preclinical Pipeline Candidates

The Company continues to advance pre-clinical assets in respiratory syncytial virus in partnership with GSK and pursue HIV cure in collaboration with the Bill & Melinda Gates Foundation.
Corporate Update

On August 1, 2024 the Company announced an exclusive worldwide license to three clinical-stage masked T-cell engagers (TCEs) with potential applications in a range of cancers, as well as the exclusive use of the proprietary PRO-XTEN masking platform for oncology and infectious disease. The Company announced closing of the agreement with Sanofi on September 9, 2024.
Key employees from Sanofi, possessing extensive scientific and development expertise in TCEs, and in-depth experience with the PRO-XTEN platform, joined the Company following the closing of the agreement.
On August 1, 2024 the Company announced the phase-out of clinical programs in influenza, COVID-19, and its T-cell based viral vector platform. The Company is seeking partners to advance these clinical programs through further development. Additionally, the Company announced a workforce reduction of approximately 25%, or approximately 140 employees, and expects to end 2024 with approximately 435 employees – a decrease of approximately 200 from its peak headcount in the second quarter of 2023.
On September 10, 2024, the Company announced the appointment of Jason O’Byrne as Executive Vice President and Chief Financial Officer, effective October 2, 2024. Mr. O’Byrne is an accomplished executive with more than 20 years of finance and operations experience, and brings leadership in capital allocation and formation, corporate strategy and operational excellence.
The Company will host two virtual investor events instead of the previously scheduled R&D Day in the fourth quarter of 2024. The first event, focusing on our hepatitis programs, will be held in November 2024, following the AASLD conference, and will provide detailed updates on our hepatitis delta and hepatitis B programs. In the first quarter of 2025, the Company will share initial clinical data for our masked T-cell engager programs during a second dedicated investor event.
Third Quarter 2024 Financial Results

Cash, Cash Equivalents and Investments: As of September 30, 2024, the Company had approximately $1.19 billion in cash, cash equivalents and investments, representing a decrease of approximately $245.1 million during the third quarter of 2024. The decrease includes a $103.7 million upfront payment made to Sanofi upon the closing of the agreement and a $75.0 million escrowed milestone payment reclassified to restricted cash. The escrowed milestone is subject to VIR-5525 achieving "first in human dosing" by 2026. Excluding the impact of the Sanofi agreement, the decrease in cash, cash equivalents and investments in the third quarter was approximately $66.4 million.

Revenues: Total revenues for the quarter ended September 30, 2024, were $2.4 million compared to $2.6 million for the same period in 2023.

Cost of Revenue: Cost of revenue was nominal for the third quarter of 2024 and 2023.

Research and Development Expenses (R&D): R&D expenses for the third quarter of 2024 were $195.2 million, which included $8.9 million of non-cash stock-based compensation expense, compared to $145.0 million for the same period in 2023, which included $15.8 million of non-cash stock-based compensation expense. The increase was primarily driven by $102.8 million of the Sanofi upfront payment being recognized as in-process research and development expense, partially offset by lower clinical development costs and manufacturing costs associated with the discontinued flu asset, VIR-2482.

Selling, General and Administrative Expenses (SG&A): SG&A expenses for the third quarter of 2024 were $25.7 million, which included $7.8 million of non-cash stock-based compensation expense, compared to $40.9 million for the same period in 2023, which included $11.1 million of non-cash stock-based compensation expense. The decrease was largely related to cost savings initiatives implemented during the second half of 2023.

Restructuring, long-lived assets impairment and related charges: Restructuring, long-lived assets impairment and related charges for the third quarter of 2024 were $12.7 million compared to $3.4 million for the same period in 2023. The increase was primarily driven by severance charges incurred related to our strategic restructuring announcement in August 2024 and to a lesser extent right-of-use asset impairment charges related to the closing of our Portland, Oregon facility, which was previously announced on December 13, 2023.

Other Income: Other income for the third quarter of 2024 was $17.8 million compared to $20.1 million for the same period in 2023. The decrease was primarily due to lower interest income.

(Provision for) Benefit from Income Taxes: Provision for income taxes for the third quarter of 2024 was $0.2 million compared to a benefit from income taxes of $3.2 million for the same period in 2023.

Net Loss: Net loss attributable to Vir for the third quarter of 2024 was $(213.7) million, or $(1.56) per share, basic and diluted, compared to a net loss of $(163.4) million, or $(1.22) per share, basic and diluted for the same period in 2023.

2024 Financial Guidance

The Company has updated its operating expense guidance for the full-year 2024, which includes the upfront in-process research and development expense associated with the clinical-stage T-cell engagers licensed through its agreement with Sanofi:

(in $ millions)

GAAP operating expense range:

$

660

to

$

680

The following expenses are included in the GAAP operating expense range:

Upfront payment to Sanofi recognized as R&D expense in the third quarter of 2024

$103

Stock-based compensation expense

$

90

to

$

80

Restructuring charges*

$

40

to

$

30

* Restructuring charges include employee severance cash payouts, as well as non-cash expense related to the closing of two R&D sites previously announced on December 13, 2023.

The GAAP operating expense guidance does not include the effect of GAAP adjustments caused by events that may occur subsequent to the publication of this guidance, including, but not limited to, business development activities, litigation, in-process R&D impairments, and changes in the fair value of contingent considerations.

Conference Call

Vir will host a conference call to discuss the third quarter results at 1:30 p.m. PT / 4:30 p.m. ET today. A live webcast will be available on View Source and will be archived on www.vir.bio for 30 days.

About Tobevibart (VIR-3434)

Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen. It is designed to inhibit the entry of hepatitis B and hepatitis delta viruses into hepatocytes, and to reduce the level of circulating viral and subviral particles in the blood. Tobevibart, which incorporates Xencor’s Xtend and other Fc technologies, has been engineered to have an extended half-life and was identified using Vir’s proprietary monoclonal antibody discovery platform. Tobevibart is administered subcutaneously, and it is currently in clinical development for treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta.

About Elebsiran (VIR-2218)

Elebsiran is an investigational hepatitis B virus-targeting small interfering ribonucleic acid (siRNA) designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. Current data indicates that it has the potential to have direct antiviral activity against hepatitis B virus and hepatitis delta virus. Elebsiran is administered subcutaneously, and it is currently in clinical development for treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta. It is the first asset in Vir’s collaboration with Alnylam Pharmaceuticals, Inc. to enter clinical studies.

About VIR-5818, VIR-5500, VIR-5525

VIR-5818, VIR-5500, VIR-5525 are investigational, clinical candidates currently being evaluated for the treatment of solid tumors. These assets leverage the PRO-XTEN masking technology with three different T-cell engagers (TCEs) targeting HER2, PSMA, and EGFR, respectively.

TCEs are powerful anti-tumor agents that direct the immune system, specifically T-cells, to destroy cancer cells. The PRO-XTEN masking technology is designed to keep the TCEs inactive (or masked) until they reach the tumor microenvironment, where tumor-specific proteases cleave off the mask and activate the TCEs leading to killing of cancer cells. By driving the activity exclusively to the tumor microenvironment, we aim to circumvent the traditionally high toxicity associated with TCEs and increase their efficacy and tolerability. Additionally, the mask also helps drug candidates stay in the bloodstream longer in their inactive form, allowing them to better reach the site of action and potentially allowing more convenient dosing regimens for patients and clinicians.

On October 31, 2024 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics ("Molecular Partners" or the "Company"), reported corporate highlights and unaudited financial results for the third quarter of 2024 (Press release, Molecular Partners, OCT 31, 2024, View Source [SID1234647606]).

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"In the last quarter we continued to execute our plan to bring our first Radio-DARPin program to IND submission, and into the clinics. DLL3 remains a highly interesting target that is gaining significant attention. Our team presented additional preclinical data showing that MP0712 is safe and efficacious in a highly relevant tumor model, with DLL3 expression levels matching those in human tumors," said Patrick Amstutz, Ph.D., Molecular Partners’ Chief Executive Officer. "In addition, we strengthened our relationship with our partner Orano Med, ensuring that both parties will have the opportunity to bring two Radio-DARPin products to market, for a total of four. Lastly our recent capital raise allows us additional financial flexibility into 2027 with participation from new, specialized investors and supportive existing investors."

Financial and Business Outlook
For the full year 2024, at constant exchange rates, the Company reiterates its guidance for total expenses of CHF 65–70 million. Approximately CHF 7 million of this will be non-cash effective costs for share-based payments, pension accounting and depreciation. This guidance does not include any potential receipts from R&D collaborators.
With CHF 143.6 million in cash and short-term time deposits and no debt as of September 30, 2024, the Company expects to be funded into 2027, excluding any potential receipts from R&D collaborators.
On October 25, 2024, Molecular Partners announced the pricing of an underwritten offering in the US of 3’642’988 American Depositary Shares (ADSs) representing 3’642’988 ordinary shares at an offering price of USD 5.49 per ADS. The total gross proceeds amount to approximately USD 20 million. The offering included participation from a new investor HBM Healthcare Investments Ltd, which is a leading healthcare investor, as well as multiple existing investors. Leerink Partners and TD Cowen acted as joint bookrunning managers for the offering. LifeSci Capital acted as lead manager for the offering, and Zürcher Kantonalbank (ZKB) served as settlement agent. Molecular Partners currently intends to use the net proceeds from this offering, together with its existing cash and cash equivalents, for development and expansion of its radiopharmaceutical pipeline and platform (Radio-DARPin Therapeutics) and for working capital and other general corporate purposes. Subsequent to the offering, the Company has (proforma) cash and short-term time deposits in the amount of CHF 158 million, with 40,363,095 issued shares.

Research & Development Highlights

MP0712 and Radio-DARPin Therapy (RDT): Preparing for IND submission and clinical entry in 2025
Molecular Partners has leveraged the intrinsic properties of DARPins, such as small size, high affinity and specificity, to engineer Radio-DARPins as ideal vector candidates for radiopharmaceutical therapeutics and to create a Radio-DARPin Therapy (RDT) platform amenable to a broad range of tumor targets. Historically, small protein-based vectors faced challenges with kidney accumulation and toxicity, as well as suboptimal tumor uptake. Molecular Partners’ RDT platform addresses these limitations with its half-life extension technologies and surface engineering approaches, while preserving the advantages of the small protein format.

MP0712 is a 212Pb-based Radio-DARPin Therapeutic (RDT) candidate targeting the tumor-associated protein delta-like ligand 3 (DLL3). MP0712 is being co-developed with Orano Med, a clinical stage pioneer of targeted alpha therapies using the lead isotope 212Pb. Molecular Partners and Orano Med anticipate initiating first-in-human studies in 2025, pending regulatory clearance. Initial clinical data of MP0712 is also anticipated in 2025.

In October 2024, Molecular Partners presented new in vivo data at the EANM Congress. MP0712 demonstrated high affinity and specificity for DLL3 and a favorable safety profile. DLL3 is a highly relevant target for radiopharmaceutical therapy due to its abundant expression in tumors of patients with small cell lung cancer (present in >85% of tumors) and other aggressive neuroendocrine tumors, while expression in healthy tissues is low. MP0712 led to attractive tumor to kidney (T:K) ratios of >2 in biodistribution studies across several models, and to strong and dose-dependent efficacy in mice bearing established tumors with clinically-relevant levels of DLL3 expression and at a clinically-relevant dose.
On October 22, 2024, Molecular Partners and Orano Med signed a revised and strengthened agreement to co-develop 212Pb-based Radio-DARPin Therapeutics. This revision builds on the original agreement signed in January 2024. Under the revised agreement, both companies will co-develop four Radio-DARPin programs; each company will have the right to commercialize two programs (previously one each). Molecular Partners will hold commercialization rights to the second nominated Radio-DARPin candidate, in addition to rights to the first program MP0712.

In addition to the updates above, Molecular Partners continued to progress its RDT portfolio with projects through a partnership with Novartis, and is evaluating additional targets for RDT programs. An update on the broader RDT portfolio is expected to be shared in the first half of 2025.

MP0533 (multispecific T cell engager)

MP0533, a novel tetra-specific T cell-engaging DARPin, is currently being evaluated in a Phase 1/2a clinical trial for patients with relapsed/refractory acute myeloid leukemia (r/r AML) and myelodysplastic syndrome/AML (MDS/AML) (ClinicalTrials.gov: NCT05673057). The trial is currently enrolling patients in Cohort 8. MP0533’s mode of action is designed to preferentially kill AML cells (blasts, leukemic progenitor and stem cells) that express any combination of the three cell surface antigens CD33, CD123, and CD70, while sparing healthy cells, which tend to express only one or none of these targets. The immune activation against the malignant cells is achieved through CD3-mediated T-cell engagement.

As shared in August 2024, MP0533 showed an acceptable tolerability profile with the majority of adverse events reported being infusion-related reactions and cytokine release syndrome. Based on this observed tolerability profile and initial antitumor activity data, and following discussion with treating physicians and key opinion leaders, Molecular Partners is amending the protocol to further increase dosing and improve the exposure profile of MP0533.
Molecular Partners plans to present the next clinical update of the program at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego on December 7–10, 2024, and data following the protocol amendment are expected in 2025.

Switch-DARPin Platform (next-gen immune cell engagers)
The Switch-DARPin platform provides a logic-gated "on/off" function (the "Switch") to multi-specific DARPin candidates leading to target activation only in the presence of defined antigens. The objective is conditional activation of a targeted immune response.

MP0621 is a Switch-DARPin candidate designed to induce killing of hematopoietic stem cells as a next-generation conditioning regimen for HSCT. The in vivo proof-of-mechanism data, as presented at EHA (Free EHA Whitepaper) 2024, demonstrate that MP0621 could be an efficient next-generation conditioning regimen for autologous HSCT. At present, the non-human primate data do not indicate that MP0621 would serve as a treatment for AML. As Molecular Partners’ portfolio strategy prioritizes therapeutic candidates for oncology, MP0621 is being evaluated for partnering. The Company plans to present a preclinical update on MP0621 at ASH (Free ASH Whitepaper) 2024.

Proof-of-concept preclinical data on an additional Switch-DARPin candidate, namely a CD3 Switch-DARPin T cell engager for solid tumors, will be presented at SITC (Free SITC Whitepaper) 2024 on November 9, 2024. The CD3 Switch-DARPin targets the highly validated immunostimulatory protein CD3 to deliver a T cell-engager (TCE) mechanism with enhanced function via engagement of additional receptors on the surface of T cells. TCEs are a powerful class of immuno-oncology therapies but have faced a range of challenges such as toxicity, poor T cell fitness and immune suppression, particularly in solid tumors. By employing a multi-specific Switch approach, Molecular Partners aims to broaden the therapeutic space for T cell engagers.

MP0317 (localized agonist)

MP0317 is a CD40 agonist designed to activate immune cells specifically within the tumor microenvironment (TME) by anchoring to fibroblast activation protein (FAP) which is expressed in high amounts around tumors. This tumor-localized approach has the potential to deliver greater efficacy with fewer side effects compared to systemic CD40-targeting therapies.

In September 2024, the Company presented details of the transcriptomic analysis from its completed Phase 1 study at CICON 2024. The analysis of patient biopsies pre- and post-treatment with MP0317 showed that this molecule remodels the tumor microenvironment by inducing infiltration of B, plasma, dendritic, and T follicular helper cells.
Molecular Partners plans to share a comprehensive biomarker analysis of its completed Phase 1 study at SITC (Free SITC Whitepaper) on November 9, 2024.

The positive Phase 1 data support further clinical evaluation of MP0317 in combination with complementary anticancer therapies and demonstrated the ability of the DARPin design to deliver on a targeted, tumor-localized CD40 activation mechanism. Molecular Partners is in discussion with leading academic centers regarding potential investigator-initiated combination trials.