On January 30, 2025 Ypsilon Therapeutics, a portfolio company of 82VS, Alloy’s venture studio, reported the company has been awarded $2.7 million in seed funding from CPRIT (Press release, Ypsilon Therapeutics, JAN 30, 2025, View Source [SID1234649975]). Ypsilon will use the grant to rapidly advance its lead therapeutic program, a next generation T-cell receptor mimic (TCRm) antibody, to drug candidate nomination, furthering its mission to deliver breakthrough treatments for patients with difficult to treat solid tumors such as triple negative breast cancer, non-small cell lung cancer, and gastric cancer. Ypsilon’s CPRIT grant, one of nine awards selected from 90 applicants, will also fund the critical establishment of the company’s operations in Texas.

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"We founded Ypsilon to leverage the incredible specificity of how TCRs interact with proteins on the surface of cancer cells to enable new ways to target and treat cancer with high precision and efficacy"

TCRms are an emerging class of antibody-based drugs that have been engineered to bind with high specificity to intracellular protein fragments presented on the surface of cells by major histocompatibility complex molecules (pMHC). Compared to traditional antibodies that only target soluble or cell surface proteins, TCRms enable targeting of an expanded set of intracellular proteins including cancer testes antigens and other oncogenic drivers that are highly specific to tumor cells. Ypsilon is developing bispecific T cell engager molecules that can bind tumor associated pMHC complexes and drive potent cell killing.

"We founded Ypsilon to leverage the incredible specificity of how TCRs interact with proteins on the surface of cancer cells to enable new ways to target and treat cancer with high precision and efficacy," said Dr. Dongxing Zha, CEO/Co-Founder of Ypsilon and CTO of TCR Discovery and Engineering at Alloy. "The award from CPRIT will allow us to advance our lead TCRm program to drug candidate nomination and support our move to Texas, where I spent seven years of my career at the MD Anderson Cancer Center. I look forward to further contributing to the growth and success of the Texas biotech community."

Ypsilon’s innovative TCRm programs leverage Alloy’s Keyway TCR Discovery platform, which was developed by Dr. Zha. Alloy’s Keyway TCR Discovery platform is the first fully-integrated service offering to unlock the therapeutic potential of a variety of T-cell receptor-based modalities. Keyway’s end-to-end TCRm discovery service includes pMHC production, antibody discovery in Alloy’s suite of transgenic humanized mice, specificity screening, and generation of optimized T cell engagers. The combined support from CPRIT, 82VS, and Alloy Therapeutics strengthens the impact of Ypsilon’s research in addressing critical patients.

"The CPRIT grant is a significant endorsement of Ypsilon’s approach to developing novel cancer therapeutics and highlights 82VS’s ability to identify and launch companies with strong potential to secure external funding," said Errik Anderson, CEO and Founder of Alloy Therapeutics and General Partner at 82VS. "Ypsilon is leveraging the Keyway platform within Alloy, showcasing our commitment to democratizing access to advanced biologics discovery services and cutting-edge technologies. We’re confident that Ypsilon’s move to Texas will not only strengthen the state’s world-class biomedical community, but also enhance our ability to discover and support promising Texas-based companies through the 82VS portfolio."

On January 30, 2025 Takeda (TOKYO:4502/NYSE:TAK) reported earnings results for the third quarter of fiscal year 2024 (nine months ended December 31, 2024) showing continued advancement of its Growth & Launch Products, which delivered double-digit growth of 14.6% at CER (Press release, Takeda, JAN 30, 2025, View Source [SID1234649974]). The company has upgraded its full year outlook for growth, reflecting strong year-to-date product performance and OPEX efficiencies, as well as revised foreign exchange assumptions.

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Takeda continues to advance multiple late-stage programs and is on track for three Phase 3 data readouts within the calendar year 2025. The company expects three regulatory filings in FY2025-FY2026 and five additional regulatory filings in FY2027-FY2029. Six of these late-stage programs are estimated to have the potential to generate peak revenues ranging from USD 10 billion to 20 billion in total and contribute to long-term growth.

Takeda also announced today its decision to buy back shares up to JPY 100.0 billion, underscoring confidence in its strong business momentum and commitment to shareholder returns. For details, see release: Takeda Announces Acquisition of Own Shares

Takeda chief financial officer, Milano Furuta, commented:
"We are raising our Management Guidance and reported & Core forecasts for the full year, pivoting to a growth outlook for revenue and operating profit on the strength of product momentum and OPEX efficiencies from our efficiency program. We are confident that we will grow our Core Operating Profit margin this fiscal year.

"As highlighted at our R&D Day in December 2024, we are on track to three Phase 3 data readouts within calendar year 2025, strengthening confidence in our long-term growth outlook.

"The announcement of our new share buyback program, approved by Takeda’s Board of Directors, demonstrates our commitment to shareholder returns."

FINANCIAL HIGHLIGHTS for FY2024 Q3 YTD Ended December 31, 2024

(Billion yen, except percentages and per share amounts)

FY2024 Q3 YTD

FY2023 Q3 YTD

vs. PRIOR YEAR

(Actual % change)

Revenue

3,528.2

3,212.9

+9.8%

Operating Profit

417.5

224.1

+86.3%

Net Profit

211.1

147.1

+43.5%

EPS (Yen)

134

94

+42.1%

Operating Cash Flow

835.0

437.8

+90.8%

Adjusted Free Cash Flow (Non-IFRS)

568.3

36.3

+1,466%

Core (Non-IFRS)

(Billion yen, except percentages and per share amounts)

FY2024 Q3 YTD

FY2023 Q3 YTD

vs. PRIOR YEAR

(Actual % change)

vs. PRIOR YEAR

(CER % change)

Revenue

3,528.2

3,212.9

+9.8%

+4.5%

Operating Profit

1,006.3

865.6

+16.3%

+10.1%

Margin

28.5%

26.9%

+1.6pp

―

Net Profit

698.9

643.6

+8.6%

+1.9%

EPS (Yen)

443

412

+7.5%

+0.9%

FY2024 Outlook
Updating Full Year Management Guidance and Reported and Core Forecasts

Takeda has upgraded its FY2024 Management Guidance, primarily driven by product momentum and OPEX savings. In addition, and also reflecting revised foreign exchange assumptions for the year, Takeda has raised its FY2024 reported and Core forecasts from the previous forecast. For more details, see release: Notice of the Revised Forecast of Consolidated Financials for FY2024 (IFRS)

FY2024 Management Guidance Core Change at CER (Non-IFRS)

FY2024 PREVIOUS
MANAGEMENT GUIDANCE
(October 2024)

FY2024 REVISED
MANAGEMENT GUIDANCE
(January 2025)

Core Revenue

Flat to slightly increasing

Low-single-digit % increase

Core Operating Profit

Mid-single-digit % decline

Low-single-digit % increase

Core EPS (Yen)

Approx 10% decline

Flat to slightly declining

FY2024 Reported and Core Forecasts

(Billion yen, except percentages and per share amounts)

FY2024
PREVIOUS FORECAST

(October 2024)

FY2024

REVISED FORECAST

(January 2025)

Revenue

4,480.0

4,590.0

Core Revenue (Non-IFRS)

4,480.0

4,590.0

Operating Profit

265.0

344.0

Core Operating Profit (Non-IFRS)

1,050.0

1,150.0

Net Profit

68.0

118.0

EPS (Yen)

43

75

Core EPS (Yen) (Non-IFRS)

456

507

Adjusted Free Cash Flow (Non-IFRS)

400.0-500.0

550.0-650.0

Annual Dividend per Share (Yen)

196

196

Positive Momentum in High-Value, Late-Stage Pipeline
The company is building strong momentum with its high-value, late-stage programs. The transformative value these programs can deliver to patients, as well as the significant revenue potential through 2030 and beyond, were presented at the R&D Day event held in December 2024.

Among the multiple late-stage programs presented, the company expects three Phase 3 data readouts in the calendar year 2025 with filings anticipated in FY2025-FY2026 for the following programs and indications:

oveporexton (TAK-861) for the treatment of narcolepsy type 1,
zasocitinib for the treatment of psoriasis, and
rusfertide for the treatment of polycythemia vera, a rare chronic blood disorder
Moreover, five additional indication filings for late-stage programs are on pace for FY2027-FY2029.

zasocitinib for the treatment of psoriatic arthritis,
mezagitamab for treatments of immune thrombocytopenia (ITP), a rare immune-mediated bleeding disorder, and immunoglobulin A nephropathy (IgAN), a chronic progressive autoimmune mediated kidney disease,
fazirsiran for the treatment of alpha-1 antitrypsin deficiency-associated liver disease, and
elritercept for the treatment of anemia associated with myelodysplastic syndrome
Beyond its high-value, late-stage pipeline, Takeda will continue advancing its early-stage pipeline and focusing on strategic business development opportunities, to deliver treatments that have the potential to change patients’ lives.

Additional Information About Takeda’s FY2024 Q3 YTD Results
For more details about Takeda’s FY2024 Q3 YTD results, commercial progress, pipeline updates and other financial information, including key assumptions in the FY2024 forecast and management guidance as well as definitions of non-IFRS measures, please refer to Takeda’s FY2024 Q3 investor presentation (available at View Source)

On January 30, 2025 Owkin, the first end-to-end AI-biotech that uses agentic AI to revolutionize drug discovery, development, and diagnostics, reported that the first patient has been dosed in its Phase I clinical trial of OKN4395 on January 22, 2025 (Press release, Owkin, JAN 30, 2025, View Source [SID1234649973]). OKN4395 builds upon well-characterized EP2/EP4 inhibition, through a newly identified and equipotent inhibition of DP1. The clinical significance of this first-in-class triple inhibition is being evaluated in this trial.

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AI-optimized study design

Owkin’s proprietary K1.0 Operating System was instrumental in advancing OKN4395 from asset selection through to clinical development. By building a detailed biological understanding of the EP2/EP4/DP1 targets and their complex mechanisms of action, Owkin’s AI operating system was used to optimize the clinical development strategy. The program integrates Owkin’s expertise in AI-driven indication selection, external control arms (digital twins) for early anti-tumor activity insights in Phase I, and biomarker-led patient subtyping to enhance the probability of clinical success.

Thomas Clozel, MD, CEO & Co-founder of Owkin, said: "OKN4395 reflects not only a decade of discovery efforts by Idorsia and its collaborators but also exemplifies the transformative power of Owkin’s K1.0 Operating System. This milestone underscores our ability to rapidly translate a promising asset into an AI-optimized clinical program."

A first-in-class asset: OKN4395

Prostaglandins E2 and D2 (or PGE2, PGD2) are hormone-like molecules produced naturally in the body, and are the natural ligands for prostanoid receptors EP2, EP4, and DP1, respectively. The PGE2/EP2/EP4 and PGD2/DP1 pathways are both known to be immunosuppressive1,2. Well-described in oncology, hyperactivity of the PGE2/EP2/EP4 pathway in certain cancers allows them to avoid the immune system’s effector mechanisms, leading to progression and resistance through tumor growth or metastasis1.

OKN4395 is the first compound in the clinic to selectively inhibit EP2, EP4, and DP1 receptors. This novel mechanism offers the potential to restore immune function, providing transformative treatment options for patients with advanced solid tumors.

The INVOKE Study (OKN-4395-121)

INVOKE is a global, multicenter, Phase Ia/1b, first-in-human, open-label trial evaluating OKN4395 in patients with advanced solid tumors. Phase Ia primarily assesses safety and tolerability through dose escalation of OKN4395 as both a monotherapy and in combination with pembrolizumab. Phase Ib will expand into a further four cohorts, and assess preliminary anti-tumor activity, as well as safety and extensive exploratory analyses.

On January 30, 2025 Orion Corporation ("Orion"), a globally operating pharmaceutical company, and Invenra Inc., an innovative biotechnology company with proprietary technologies for discovering novel therapeutics, reported that they have entered into a research collaboration to discover bispecific antibodies using Invenra’s B-Body platform (Press release, Orion, JAN 30, 2025, View Source [SID1234649972]).

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Under the terms of the agreements, Invenra will leverage its B-Body bispecific antibody platform from monoclonal antibody discovery to optimized panels of bispecific leads. Orion will be responsible for the selection of targets and will be solely responsible for the development, manufacturing, and global commercialization of these candidates. The agreement provides Orion with commercial licenses for up to two bispecific antibodies.

"This collaboration highlights the strength and versatility of our B-Body platform in addressing complex biological challenges," said Roland Green, CEO of Invenra. "We are thrilled to work with Orion, a company that shares our commitment to delivering innovative therapies that address critical unmet medical needs."

"Partnering with Invenra represents an important step in Orion’s strategy to expand our portfolio in the bispecific antibody space," said Antti Haapalinna, Vice President, Head of External Science & Partnering R&D, Orion. "Invenra’s cutting-edge bispecific discovery platform, combined with Orion’s expertise in development and commercialization, will accelerate the creation of impactful new therapies for patients worldwide."

This discovery collaboration combines Invenra’s advanced engineering expertise in bispecific antibody discovery with Orion’s established track record in pharmaceutical innovation, setting the stage for the development of next-generation therapeutic solutions.

On January 30, 2025 Astrazeneca reported that the first patient has been dosed in the TROPION-Lung12 phase 3 trial evaluating the efficacy and safety of adjuvant DATROWAY (datopotamab deruxtecan) plus rilvegostomig or rilvegostomig monotherapy versus standard of care in patients with stage 1 adenocarcinoma non-small cell lung cancer (NSCLC) after complete surgical resection who are ctDNA-positive or have other high risk pathological features (Press release, AstraZeneca, JAN 30, 2025, View Source [SID1234649971]).

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DATROWAY is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN).

Standard treatment for stage 1 NSCLC is tumor resection, but up to 40% of patients may experience disease recurrence.1,2,3 Tumor resection is typically followed by observation but adjuvant chemotherapy and/or immunotherapy may be offered to patients with stage 1b disease who are identified to be at high risk of relapse.4 However, novel strategies to identify high risk patients are needed as well as additional treatment options in the adjuvant setting. Research suggests that ctDNA screening may help identify high risk patients who are most likely to benefit from adjuvant therapy.5,6

"After surgery for early-stage non-small cell lung cancer, there is no established consensus on adjuvant therapy. As a result, patients may either undergo observation or receive adjuvant chemotherapy and/or immunotherapy if they have stage 1b disease and are determined to be at high risk for disease recurrence," said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. "The TROPION-Lung12 trial will help us better understand the role of DATROWAY in combination with immunotherapy in the adjuvant setting as a potential treatment regimen to help prevent disease recurrence in patients with high risk stage 1 adenocarcinoma following surgery."

"With TROPION-Lung12, we are simultaneously deploying a novel strategy for identifying patients with lung cancer who are at an increased risk of disease recurrence after surgery and evaluating novel treatment options in the adjuvant setting, including rilvegostomig with and without DATROWAY," said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. "The ambitious approach in this trial underscores our commitment to both enabling more personalized treatment decisions and delivering innovative treatment options to patients with cancer."

About TROPION-Lung12
TROPION-Lung12 is a global, multicenter, three-arm, open-label phase 3 trial where patients will be randomized in a 2:1:2 ratio to evaluate the efficacy and safety of adjuvant DATROWAY (6 mg/kg) in combination with rilvegostomig (750 mg) or rilvegostomig (750 mg) monotherapy versus observation or standard of care adjuvant chemotherapy regimens in those with stage 1 (stage 1a or 1b with tumors < 4 cm) adenocarcinoma NSCLC who are ctDNA-positive (as determined by an investigational ctDNA assay) or have high risk pathological features (as determined by central pathology assessment).

The primary endpoint of TROPION-Lung12 is disease-free survival following complete tumor resection as assessed by blinded independent central review in patients treated with adjuvant DATROWAY and rilvegostomig versus those who undergo observation or receive standard of care. Key secondary endpoints include patient-reported physical functions, patient-reported quality of life outcomes, overall survival and safety.

TROPION-Lung12 will enroll approximately 660 patients in Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.

Rilvegostomig is AstraZeneca’s PD-1/TIGIT bispecific antibody. The TIGIT component of rilvegostomig is derived from the clinical-stage anti-TIGIT antibody, COM902, developed by Compugen Ltd. (Nasdaq/TASE: CGEN).

About Non-Small Cell Lung Cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.7 NSCLC is the most common type of lung cancer and adenocarcinoma is the most common subtype of NSCLC, accounting for about 40% of all lung cancer cases.8

For patients with stage 1 NSCLC, standard treatment is tumor resection and observation.4 For patients with stage 1b disease or those otherwise identified as having a high risk of relapse based on clinical or pathological features, tumor resection may be followed by adjuvant chemotherapy and/or immunotherapy.4 However, strategies to identify high risk patients are needed as well as more durable and effective treatment options in the adjuvant setting. Research suggests that screening for ctDNA in patients with stage 1 NSCLC may help identify patients most likely to benefit from adjuvant therapy and that combining an immunotherapy with an ADC has the potential to drive deeper and more durable tumor responses.5,6

TROP2 is a protein broadly expressed in the majority of NSCLC tumors.9 There is currently no TROP2 directed ADC approved for the treatment of lung cancer.10,11

About DATROWAY
DATROWAY (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, DATROWAY is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. DATROWAY is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

DATROWAY (6 mg/kg) is approved in Japan and the U.S. for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 trial.

About the DATROWAY Clinical Development Program
A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of DATROWAY across multiple cancers, including NSCLC, triple negative breast cancer and HR positive, HER2 negative breast cancer. The program includes eight phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating DATROWAY as a monotherapy and in combination with other anticancer treatments in various settings.