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 Kazia Therapeutics Limited (NASDAQ: KZIA) an oncology-focused drug development company, reported the regulatory approval and launch of a clinical trial evaluating the combination of paxalisib and immunotherapy in patients with advanced breast cancer (Press release, Kazia Therapeutics, JAN 30, 2025, View Source [SID1234649958]). This novel treatment combination offers what is believed to be a unique approach to targeting this highly aggressive and treatment-resistant type of breast cancer.

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The ABC-Pax (Advanced Breast Cancer – Paxalisib) study is the first known trial conducted to assess the safety and efficacy of paxalisib in combination with KEYTRUDA (pembrolizumab) or LYNPARZA (olaparib) in women with triple negative breast cancer. ABC-Pax is a multi-centre, open-label phase 1b study that will enroll 24 patients from top cancer centres in Queensland, Australia and patients will receive the combination therapy for up to 12 months.

The ABC-Pax study stems from pivotal research led by QIMR Berghofer scientists in collaboration with Kazia Therapeutics, which combined its drug candidate, paxalisib, with immunotherapy in pre-clinical models. The team discovered that this combination approach triggers a novel molecular program by epigenetic re-programming of dormant cancer cells, making them visible to the immune system, while also reinvigorating the immune cells to fight the tumour cells. These new preclinical data were presented at San Antonio Breast Cancer Symposium on December 12, 2024, and highlight the potential therapeutic synergies between paxalisib and checkpoint inhibitor pembrolizumab (KEYTRUDA), as well as between paxalisib and poly (ADP-ribose) polymerase inhibitor olaparib (LYNPARZA), when used in combination in a preclinical model of immunotherapy-resistant triple negative breast cancer. The clinical trial is open for enrollment at the Royal Brisbane and Women’s Hospital and plans to expand to other sites in Australia.

Kazia Therapeutics CEO, Dr John Friend, said the novel combination treatment may have the potential to transform the treatment of triple-negative breast cancer and other aggressive tumour types.

"The novelty of the science that Professor Rao has proposed with this dual combination of paxalisib and immunotherapy could advance the treatment of women with aggressive breast cancer, and we are excited to support this unique clinical study," Dr John Friend, CEO Kazia Therapeutics said.

QIMR Berghofer’s Professor Sudha Rao said, "There is no cure for triple negative breast cancer and the life expectancy for these women is tragically short. We want to identify treatments to extend the duration and quality of life of these patients. The hope is to prolong patient survival through the new combined therapy, which targets the dormant cancer cells that drive the spread and recurrence of the disease and rejuvenates the immune system to more effectively fight the cancer."

The ABC-Pax trial will also evaluate a non-invasive liquid biopsy digital pathology platform developed by Professor Rao and her team, which can monitor the behaviour of cancer cells and immune cells in real time from a blood sample.

"By regularly analysing blood samples from trial participants using our liquid biopsy digital pathology platform, we can track the effectiveness of the treatment in real time. We believe this approach represents a major advance in precision medicine by offering a faster and more accurate way to monitor patient progress," Professor Rao said.

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, 2205 Keros Therapeutics, Inc. ("Keros") (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics to treat a wide range of patients with disorders that are linked to dysfunctional signaling of the transforming growth factor-beta ("TGF-ß") family of proteins, reported that Keros’ Chair and Chief Executive Officer Jasbir S. Seehra, Ph.D., will participate in a fireside chat presentation at the Guggenheim SMID Cap Biotech Conference on Thursday, February 6, 2025 at 10:00 a.m. Eastern time (Press release, Keros Therapeutics, JAN 30, 2025, View Source [SID1234649959]).

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A live audio webcast of the fireside chat presentation will be available at
View Source and an archived replay will be accessible in the Investors section of the Keros website at View Source for up to 90 days following the conclusion of the event.

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."