On March 13, 2024 MorphoSys AG (FSE: MOR; NASDAQ: MOR) reported results for the fourth quarter and the full year 2023 (Press release, , MAR 13, 2024, View Source [SID1234641128]).

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"In 2023, we demonstrated the potential for pelabresib to shift the myelofibrosis treatment paradigm, as results from our Phase 3 MANIFEST-2 study showed that all four disease hallmarks were improved with the pelabresib and ruxolitinib combination therapy over standard of care," said Jean-Paul Kress, M.D., Chief Executive Officer of MorphoSys. "Now, in 2024, we are pleased that Novartis is committing to the future of our promising pipeline. With its ample resources, additional scientific expertise and global footprint, Novartis can help accelerate pelabresib’s potential worldwide. The acquisition process is progressing steadily, and we expect to close the proposed transaction in the first half of the year."

Novartis’ Public Takeover Offer:

On February 5, 2024, MorphoSys announced the company entered into a Business Combination Agreement with Novartis BidCo AG (formerly known as Novartis data42 AG) and Novartis AG (hereinafter collectively referred to as "Novartis") based on Novartis’ intention to submit a voluntary public takeover offer for all outstanding MorphoSys no-par value bearer shares at an offer price of € 68.00 per share in cash. The offer price corresponds to a premium of 94% and 142% on the volume-weighted average price during the last month and three months, as of the unaffected January 25, 2024, close, respectively. As part of the Business Combination Agreement with Novartis, Novartis seeks to obtain exclusive, worldwide rights to develop and commercialize pelabresib, an investigational BET inhibitor, and tulmimetostat, an investigational next-generation dual inhibitor of EZH2 and EZH1, across all indications.

The offer will contain customary closing conditions, in particular a minimum acceptance threshold of 65% of MorphoSys’ share capital and antitrust clearances. MorphoSys and Novartis have received antitrust clearance in Germany and Austria. The companies have also made antitrust filings in the U.S. under the HSR Act and continue to expect the closing to take place in the first half of 2024.

Pelabresib Highlights:

On December 10, 2023, comprehensive results from the Phase 3 MANIFEST-2 study at 24 weeks were presented during an oral presentation at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. In MANIFEST-2, the combination of pelabresib and the JAK inhibitor ruxolitinib improved all four disease hallmarks of myelofibrosis, including a significant reduction in spleen size with a response rate nearly double that of placebo plus ruxolitinib. The combination therapy showed a strong positive trend in reducing symptom burden and improvements in measures of anemia and bone marrow fibrosis, and demonstrated safety results in line with assessments from prior clinical trials.

Monjuvi/Minjuvi Highlights:

Monjuvi (tafasitamab-cxix) U.S. net product sales of US$ 24.1 million (€ 22.4 million) for the fourth quarter 2023 (Q4 2022: US$ 25.3 million (€ 24.7 million)) and US$ 92.0 million (€ 85.0 million) for the full year of 2023 (2022: US$ 89.4 million (€ 84.9 million)). Minjuvi royalty revenue of € 1.3 million for sales outside of the U.S. in the fourth quarter 2023 (Q4 2022: € 0.7 million) and € 5.4 million for the full year of 2023 (2022: € 3.0 million).

On February 5, 2024, MorphoSys also announced it entered into a Purchase Agreement to sell and transfer all rights worldwide related to tafasitamab to Incyte Corporation ("Incyte"). Under the terms of MorphoSys’ Purchase Agreement with Incyte, Incyte will obtain exclusive rights worldwide, assume full responsibility and cover all costs going forward for the development and commercialization of tafasitamab for a purchase price of US$ 25 million.

Corporate Developments:

On December 14, 2023, MorphoSys announced the completion of a share capital increase from € 34,231,943 by € 3,423,194 to € 37,655,137 through a full utilization of its authorized capital 2023-II, resulting in gross proceeds of € 102.7 million.

Financial Results for the Fourth Quarter of 2023 (IFRS):

Total revenues for the fourth quarter 2023 were € 59.0 million compared to € 81.6 million for the same period in 2022. The decrease resulted first and foremost from prior year revenues stemming from the execution of an out-licensing agreement with Novartis.

in € million*

Q4 2023

Q3 2023

Q4 2022

Q-Q Δ

Y-Y Δ

Total revenues

59.0

63.8

81.6

(8)%

(28)%

Monjuvi product sales

22.4

21.5

24.7

4%

(9)%

Royalties

34.0

34.0

29.1

0%

17%

Licenses, milestones and other

2.6

8.3

27.9

(69)%

(91)%

* Differences due to rounding.

Cost of Sales: In the fourth quarter of 2023, cost of sales was € 14.6 million compared to € 15.4 million for the comparable period in 2022.

Research and Development (R&D) Expenses: In the fourth quarter 2023, R&D expenses were € 80.3 million compared to € 94.0 million for the same period in 2022. The decrease mainly resulted from lower expenses for external services.

Selling, General and Administrative (SG&A) Expenses: Selling expenses in the fourth quarter 2023 were € 22.6 million compared to € 23.0 million for the same period in 2022. General and administrative (G&A) expenses amounted to € 22.9 million compared to € 17.5 million for the same period in 2022.

Operating Loss: Operating loss amounted to € 81.4 million in the fourth quarter 2023 compared to € 68.4 million for the same period in 2022.

Consolidated Net Loss: For the fourth quarter 2023, consolidated net loss was € 48.3 million compared to € 329.4 million for the same period in 2022.

Financial Results for the Full Year 2023 (IFRS):

Total Revenues for the full year 2023 were € 238.3 million compared to € 278.3 million in 2022. The decrease resulted first and foremost from prior year revenues stemming from the execution of out-licensing agreements with HI-Bio and Novartis. Royalties in 2023 include € 5.4 million from the sale of Minjuvi outside of the U.S. by our partner Incyte and € 111.0 million from Tremfya sales which is fully passed on to Royalty Pharma.

in € million*

2023

2022

Y-Y Δ

Total revenues

238.3

278.3

(14)%

Monjuvi product sales

85.0

84.9

0%

Royalties

116.4

99.9

17%

Licenses, milestones and other

36.9

93.5

(61)%

* Differences due to rounding.

Cost of Sales: For the full year 2023, cost of sales were € 58.4 million compared to € 48.6 million in 2022. The increase compared to the previous year is mainly due to one-off effects from write-downs on inventories in the amount of € 11.9 million recognized in 2023.

R&D Expenses: For the full year 2023, R&D expenses were € 283.6 million compared to € 297.8 million in 2022. The decrease of R&D expenses reflects our current clinical study progress as well as prioritization activities relating to our R&D portfolio.

SG&A Expenses: Selling expenses for the full year 2023 were € 81.4 million compared to € 92.4 million in 2022. The decrease is mainly due to the ongoing measures to streamline and focus sales efforts. G&A expenses amounted to € 65.8 million for 2023 compared to € 60.1 million in 2022. The increase was mainly driven by the increase in share-based payment expenses.

Operating Loss: Operating loss amounted to € 252.5 million for the full year 2023 compared to a loss of € 220.7 million in 2022.

Consolidated Net Loss: For the full year 2023, consolidated net loss was € 189.7 million compared to a net loss of € 151.1 million in 2022.

Cash and Other Financial Assets: As of December 31, 2023, the Company had cash and other financial assets of € 680.5 million compared to € 907.2 million on December 31, 2022. The liquid funds are predominantly required to advance the development of the proprietary portfolio to key clinical and regulatory milestones. The Management Board believes that the cash and other financial assets, which also incorporates the additional cash impacts from the sale of tafasitamab to Incyte as announced on February 5, 2024, will be sufficient to fund the operating activities and other cash requirements until early 2026 including the repayment of the convertible bonds. Any potential cashflows resulting from the Novartis Business Combination Agreement as announced on February 5, 2024, were not considered in the recent corporate planning.

Under the Business Combination Agreement, Novartis agreed to use all such efforts which are from the perspective of a prudent business person reasonable and appropriate to provide MorphoSys with the financial resources required following completion of the Novartis Takeover Offer to enable MorphoSys to pay any obligations of MorphoSys arising from the implementation of the Novartis Takeover Offer as and when due, for example, but not limited to the obligation from the convertible bonds and the obligations arising from the long-term incentive plans, each to the extent triggered by the completion of the Novartis Takeover Offer.

For the unlikely case that the proposed transaction with Novartis is not consummated, and MorphoSys consequently would remain a stand-alone company, management would need to assess different financing options to ensure the going-concern assumption beyond the said timeframe according to regulatory requirements. Management would then consider both anti-dilutive financing options, such as out-licensing of (pre-) clinical assets or the sale of potential future royalties, but also consider accessing the capital markets by way of issuance of new shares or share instruments (ADSs) and/ or issuance or refinancing of convertible debt.

Number of Shares: The number of shares issued totaled 37,655,137 on December 31, 2023.

Financial Guidance 2024:

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

For 2024, the Group expects R&D expenses of € 170 million to € 185 million. R&D expenses mainly represent our investments in the development of pelabresib and tulmimetostat. Selling, administrative and general expenses are expected to be between € 90 million and € 105 million. Any effects from the implementation of the Novartis takeover offer are not included in this forecast.

The overall forecast is subject to a number of uncertainties, including inflation and foreign currency effects.

Operational Outlook:

The following activity is planned for 2024:

Submit a New Drug Application for pelabresib in combination with ruxolitinib in myelofibrosis to the U.S. Food and Drug Administration (FDA) and a Marketing Authorization Application to the European Medicines Agency in the middle of 2024.
MorphoSys Group Key Figures (IFRS, end of financial year: December 31, 2023)

in € million

Q4 2023

Q4 2022

Δ

2023

2022

Δ

Revenues

59.0

81.6

(28)%

238.3

278.3

(14)%

Product Sales

22.4

24.7

(9)%

85.0

84.9

0%

Royalties

34.0

29.1

17%

116.4

99.9

17%

Licenses, Milestones and Other

2.6

27.9

(91)%

36.9

93.5

(61)%

Cost of Sales

(14.6)

(15.4)

(5)%

(58.4)

(48.6)

20%

Gross Profit

44.4

66.2

(33)%

179.9

229.6

(22)%

Total Operating Expenses

(125.8)

(134.6)

(7)%

(432.4)

(450.4)

(4)%

Research and Development

(80.3)

(94.0)

(15)%

(283.6)

(297.8)

(5)%

Selling

(22.6)

(23.0)

(2)%

(81.4)

(92.4)

(12)%

General and Administrative

(22.9)

(17.5)

31%

(65.8)

(60.1)

9%

Impairment of Goodwill

(1.6)

—

n/a

(1.6)

—

n/a

Operating Profit / (Loss)

(81.4)

(68.4)

19%

(252.5)

(220.7)

14%

Other Income

0.1

(7.8)

>(100)%

5.0

12.0

(58)%

Other Expenses

(3.9)

7.4

>(100)%

(7.1)

(15.6)

(54)%

Finance Income

174.3

325.0

(46)%

213.4

412.1

(48)%

Finance Expenses

(40.8)

249.5

>(100)%

(142.0)

(165.9)

(14)%

Income from Reversals of Impairment Losses / (Impairment Losses) on Financial Assets

(0.1)

0.4

>(100)%

0.5

—

n/a

Share of Loss of Associates accounted for using the Equity Method

(1.6)

(4.0)

(60)%

(8.2)

(4.3)

91%

Income Tax Benefit / (Expenses)

1.6

(172.7)

>(100)%

1.2

(168.6)

>(100)%

Consolidated Net Profit / (Loss)

48.3

329.4

(85)%

(189.7)

(151.1)

26%

Earnings per Share, Basic and Diluted (in €)

—

—

n/a

(5.53)

(4.42)

25%

Earnings per Share, Basic (in €)

1.28

9.64

(87)%

—

—

n/a

Earnings per Share, Diluted (in €)

1.22

8.93

(86)%

—

—

n/a

Cash and other financial assets (end of period)

680.5

907.2

(25)%

680.5

907.2

(25)%

MorphoSys will hold its conference call and webcast tomorrow, March 14, 2024, at 1:00 pm CET (12:00 pm GMT/8:00 am EDT) to present the results for the fourth quarter and the full year 2023.

Participants for the call may pre-register and will receive dedicated dial-in details to easily and quickly access the call:

View Source;linkSecurityString=637b0c07e

Please dial in 10 minutes before the beginning of the conference.

The live webcast (audio and presentation) can be directly accessed via View Source or via the Investors section under "Events & Conferences" on the MorphoSys website, www.morphosys.com; after the call, a slide-synchronized audio replay of the conference call will be available at the same location.

Consolidated Financial Statements 2023 (IFRS) are available for download at: View Source

On March 13, 2024 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported that results from the ECLIPSE study showing the effectiveness of its ShieldTM blood test for detecting colorectal cancer (CRC) in average-risk adults will be published in the March 14 issue of The New England Journal of Medicine (Press release, Guardant Health, MAR 13, 2024, View Source [SID1234641127]).

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"Over 50 million eligible Americans do not get recommended screenings for colorectal cancer, partly because current screening methods are inconvenient or unpleasant," said AmirAli Talasaz, Guardant Health co-CEO. "We believe the publication of the ECLIPSE study in The New England Journal of Medicine, one of the world’s leading medical journals, is an endorsement of the quality of our clinical data and the potential value of the Shield test. We are confident that offering an accurate blood test has the potential to significantly reduce preventable colorectal cancer deaths."

One of the largest studies of its kind, ECLIPSE (Evaluation of ctDNA LUNAR Assay In an Average Patient Screening Episode) is a 20,000+-patient registrational study to evaluate the performance of Shield compared to a screening colonoscopy. The Shield test detects colorectal cancer signals in the bloodstream from DNA that is shed by tumors, called circulating tumor DNA (ctDNA).

Highlights of the study results to be published in The New England Journal of Medicine* show that Shield demonstrated:

83% sensitivity in detecting individuals with CRC
88% sensitivity in detecting pathology-confirmed Stages I-III
Sensitivity by stage of:
65% for pathology-confirmed Stage I; 55% for clinical Stage I
100% for Stage II
100% for Stage III
100% for Stage IV
These results are on par with the performance of other guideline-recommended non-invasive screening modalities, where overall sensitivity in detecting colorectal cancer ranges from 74% to 92%.1

"More than 3 out of 4 Americans who die from colorectal cancer are not up to date with their recommended screening,2 highlighting the need for a more convenient and less invasive screening method that can overcome barriers associated with traditional options," said Daniel Chung, MD, gastroenterologist at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School. "The ECLIPSE study results published today support the use of a blood test as a screening option that could help overcome these barriers and improve CRC screening rates."

Publication of ECLIPSE follows Guardant Health’s submission of its premarket approval (PMA) application to the U. S. Food and Drug Administration (FDA) for Shield, which included key data points from the study. Since the launch of the lab-developed version of the Shield test in May 2022, it has been used by more than 20,000 people and more than 90% of patients who were prescribed the test in the real-world clinical setting completed it. One recent study showed that CRC screening rates tripled among adults who had declined prior CRC screening when they were offered Shield. The test’s sensitivity in detecting CRC, combined with this real-world adherence, suggests that Shield has the potential to detect more CRCs at a curable stage than traditional screening methods.3,4,5,6

"Colorectal cancer is highly treatable if caught in the early stages, yet more than 50 million people in the U.S. are still not completing their recommended screening with the methods available today," said Chris Evans, president of the Colon Cancer Coalition. "This publication gets us one step closer to having an additional option to offer patients – one that is both convenient and accessible—and will help us close the screening gap."

Colorectal cancer is the second-leading cause of cancer deaths in the U.S. The American Cancer Society estimates that more than 150,000 people will be diagnosed with CRC in 20247 and it is expected to become the leading cause of cancer-related deaths by 2030 in adults aged 20-49.8 More than 75% of people who die from CRC are not up to date with recommended screening,9 often due to the perception that current methods such as colonoscopy or stool-based tests are invasive, time-consuming and inconvenient. Early detection, however, is crucial. When colon cancer is found at an early stage before it has spread, the 5-year relative survival rate is 91%. If the cancer has spread to distant parts of the body, the 5-year survival rate is 13%.

"The results of the study are a promising step toward developing more convenient tools to detect colorectal cancer early while it is more easily treated," said corresponding author William M. Grady, MD, a gastroenterologist at Fred Hutchinson Cancer Center. "The test, which has an accuracy rate for colon cancer detection similar to stool tests used for early detection of cancer, could offer an alternative for patients who may otherwise decline current screening options."

* Representatives of the media who are not able to access the article content can contact [email protected].

About the ECLIPSE study

ECLIPSE is a prospective registrational study to evaluate the performance of Guardant Health’s blood test in detecting signs of CRC compared to a screening colonoscopy in average-risk adults between the ages of 45 and 84 from across the U.S. The ECLIPSE study included more than 200 clinical trial sites in rural and urban communities across 34 states. Study data includes 12% Black, 13% Hispanic and 7% Asian American populations. Enrollment among Black Americans was above average for a clinical trial, which is important given the disproportionate impact of CRC on the Black community.10

About Shield

The Shield test for colorectal cancer screening is commercially available for eligible individuals by prescription only through healthcare professionals. This LDT (Laboratory Developed Test) is intended to be complementary to, and not a replacement for, current recommended CRC screening methods. A negative result does not rule out the presence of cancer. Patients with an abnormal blood-based screening result should be referred for a diagnostic colonoscopic evaluation.

More information about the Shield test is available at bloodbasedscreening.com.

On March 13, 2024 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported that it will present findings from preclinical studies highlighting the therapeutic potential of ZL-1310, the company’s global next-generation antibody-drug conjugate (ADC) program (Press release, Zai Laboratory, MAR 13, 2024, View Source [SID1234641126]). The preclinical profile of ZL-1310 will be the focus of a poster presentation at the European Lung Cancer Congress 2024 (ELCC 2024), scheduled for March 20-23, 2024 in Prague, Czech Republic.

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ZL-1310 is a novel and promising ADC within the Zai Lab global oncology R&D pipeline, targeting the Delta-like ligand 3 (DLL3), a validated therapeutic target in the treatment of small cell lung cancer (SCLC). DLL3, which is expressed on the cell surface of most SCLC, plays a pivotal role in promoting SCLC cell proliferation, migration and invasion.

"ZL-1310 has high affinity for the target, DLL3, and releases its payload both intracellularly and in the tumor microenvironment, also allowing for bystander effect of its camptothecin-derived payload," said Rafael G. Amado, M.D., president, head of Global Oncology Research and Development, Zai Lab. "The encouraging preclinical data we will present at ELCC 2024 formed the basis for the ZL-1310 Phase 1 clinical trial that we initiated in January of this year."

Data from the preclinical IND-enabling studies which will be shared at ELCC 2024 indicate that ZL-1310 exhibits a strong and specific binding to DLL3 on the cell surface, leading to internalization, cell cycle arrest and the induction of apoptosis in tumor cells. In-vivo, ZL-1310 effectively suppressed the growth of established human tumors in a dose-dependent manner in both cancer cell-derived (CDX) and SCLC patient sample-derived (PDX) xenograft models.

ZL-1310 was discovered with MediLink Therapeutics’ proprietary TMALIN platform, a next-generation ADC platform designed to leverage the tumor microenvironment to overcome the challenges with current ADC drugs. Zai Lab entered a partnership and exclusive worldwide license agreement with MediLink in April 2023. Subsequently, in January 2024, Zai Lab initiated a global Phase 1 study of ZL-1310 in patients with relapsed and refractory SCLC who have progressed after platinum-based treatment.

Details regarding the poster presentation at ELCC 2024 are as follows:

Title: Development and characterization of a novel DLL3-targeting antibody drug conjugate (ADC) for the treatment of solid tumors
Presenter: Linda N Liu, Senior Vice President, Biologics Discovery, Zai Lab
Date/Time: Friday, March 22, 2024, 12:00 PM – 12:45 PM CET
Location: Prague Congress Centre, Congress Hall Foyer

About Small Cell Lung Cancer (SCLC) and Neuroendocrine Tumors

SCLC and neuroendocrine tumors are diseases with significant unmet medical needs globally. There are over 300,000 SCLC annual incidences globally.1 More than 88% of SCLC patients overexpress DLL3 and could benefit from targeted therapeutic agents.2 In addition, DLL3 is a promising target highly expressed in several tumors with neuroendocrine features. There are approximately 171,000 people living with neuroendocrine tumors in the United States, and the numbers are continuing to increase, but the treatment options remain limited.

On March 13, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage cell and gene therapy company advancing a new class of treatments for patients with cancer and rare diseases, reported the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for the treatment of multiple myeloma to P-BCMA-ALLO1, a novel BCMA-targeted allogeneic, T stem cell memory (TSCM)-rich chimeric antigen receptor (CAR)-T therapy candidate (Press release, Poseida Therapeutics, MAR 13, 2024, View Source [SID1234641125]). The Company is investigating P-BCMA-ALLO1 in partnership with Roche for the treatment of relapsed/refractory multiple myeloma (RRMM).

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"The Orphan Drug Designation for P-BCMA-ALLO1 underscores the high unmet medical need for a rapid and accessible off-the-shelf allogeneic CAR-T therapy for patients with multiple myeloma," said Kristin Yarema, Ph.D., President and Chief Executive Officer of the Company. "This designation further validates our belief that TSCM-rich allogeneic CAR-T therapies may potentially offer the optimal combination of clinical results, on-demand availability, and high-volume production, while supporting broader access to CAR-T therapies. We look forward to continuing our work on the Phase 1 study of P-BCMA-ALLO1 and plan to share further clinical updates in 2024."

The Company is currently evaluating P-BCMA-ALLO1 in a Phase 1 clinical trial and recently shared positive early safety and preliminary efficacy data at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2023. Data highlighted at the meeting showed that P-BCMA-ALLO1 was a well-tolerated off-the-shelf therapy with a favorable emerging safety profile, delivered to 100% of patients in the intent-to-treat population with no use of bridging chemotherapy or other anti-myeloma bridging therapies. Preliminary data presented at ASH (Free ASH Whitepaper) also showed allogeneic TSCM-rich CAR-T cells trafficking to bone marrow, differentiating to cell-killing effector T cells and persisting at least 6 weeks after treatment, which support the hypothesis of cell persistence at tumor-relevant sites.

The Company will present data on a subset of recently enrolled patients refractory to initial BCMA targeting therapy in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in San Diego on April 8, 2024, 9:00 AM to 12:30 PM PT.

Subject to coordination with Roche, the Company plans to provide an additional clinical update on the P-BCMA-ALLO1 program at a scientific meeting in the second half of 2024.

The FDA’s Orphan Drug Designation program provides orphan status to drugs or biologics intended for the prevention, diagnosis, or treatment of diseases that affect fewer than 200,000 people in the United States. Sponsors of medicines that are granted Orphan Drug Designation are entitled to certain incentives, including tax credits for qualified clinical trials, prescription drug user-fee exemptions, and potential seven-year marketing exclusivity upon FDA approval.

About P-BCMA-ALLO1

P-BCMA-ALLO1 is an allogeneic CAR-T product candidate licensed to Roche targeting B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma. This allogeneic program includes a VH-based binder that targets BCMA and clinical data presented at ASH (Free ASH Whitepaper) in December 2023 support the Company’s belief that TSCM-rich allogeneic CAR-Ts have the potential to offer effective, safe, and reliable treatment addressing unmet needs in multiple myeloma. Additional information about the Phase 1 study is available at www.clinicaltrials.gov using identifier: NCT04960579.

On March 13, 2024 Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small-molecule therapies that address emerging targets in oncology, reported its 2023 fiscal year and provides a corporate update (Press release, Ryvu Therapeutics, MAR 13, 2024, View Source [SID1234641124]).

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Pawel Przewiezlikowski, co-founder, largest shareholder, and Chief Executive Officer of Ryvu Therapeutics, said:

– In 2023, we made significant progress in all key business areas and look forward to multiple catalysts in 2024. We have already started two Phase II studies of RVU120, and around mid-year, we plan to launch two more Phase II studies in hematology. By the end of the year, we plan to enroll more than 100 patients across these clinical trials. We also plan to launch a new Phase II study of MEN1703 (SEL24) in DLBCL, which is being developed under a license agreement with the Menarini Group. Study start-up activities for new trials of both RVU120 and MEN1703 are proceeding quickly.

Krzysztof Brzozka, Ph.D., Executive Vice President, and Chief Scientific Officer, said:

– We are pleased with the significant progress made in our early-phase projects. Among the most advanced projects from our synthetic lethality platform – PRMT5 and WRN – we plan to identify a clinical candidate in 2024. We are also seeing progress in the programs being developed by our partners – particularly BioNTech and Exelixis. We were excited to achieve the second milestone in the Exelixis collaboration, and we look forward to presenting data on our synthetic lethality assets and novel platform at AACR (Free AACR Whitepaper).

2023 SUMMARY AND RECENT CORPORATE EVENTS

RVU120 clinical development plan

In 2023 Ryvu prepared for the launch of two Phase II RVU120 trials, which then initiated in early 2024: 1) RVU120 as monotherapy in genetically defined cohorts of patients with relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes (HR-MDS, RIVER-52 study), and 2) RVU120 in combination with venetoclax for patients with relapsed/ refractory AML (RIVER-81 study).
Ryvu will financially support the REMARK study’s Phase II clinical trial of RVU120 in patients with low-risk myelodysplastic syndromes (LR-MDS). REMARK will be conducted as an investigator-initiated study through the EMSCO network, with Prof. Uwe Platzbecker, a globally renowned expert in the field of LR-MDS, as the Coordinating Principal Investigator. Start-up activities have already been launched, and patient enrollment will start in mid-2024.
Study start-up is also underway for POTAMI-61, a Phase II study evaluating the efficacy of RVU120 in patients with myelofibrosis (MF). Initiation of patient recruitment is scheduled for mid-2024.
Translational research on RVU120 in solid tumors will continue, including combination studies, as well as academic collaborations in the areas of medulloblastoma (MB) and sarcoma-related research.
The company plans to enroll more than 100 patients across all RVU120 Phase II trials this year and aims to present initial Phase II data by the end of 2024.
RVU120’s updated clinical development plan includes studies (RIVER-52, RIVER-81, and POTAMI-61) that could lead to three drug approvals between 2026 and 2027.
Key data presented during 2023 conferences

In 2023, Ryvu Therapeutics presented data from the RVU120 program at several international conferences, including EHA (Free EHA Whitepaper) 2023, ESMO (Free ESMO Whitepaper) 2023, and ASH (Free ASH Whitepaper) 2023:

RVU120 monotherapy demonstrated clinical activity in a Phase Ib study in which 50% of evaluable patients with r/r AML or HR-MDS achieved clinical benefit, including a complete response, morphologically leukemia-free status, clinically significant reduction of blasts including reductions that allowed bridging to a bone marrow transplantation, two-year disease stabilization, hematologic improvements, as well as reduction in bone marrow fibrosis.
In particular, early signs of efficacy were observed in patients with an NPM1 mutation, DNMT3a mutation, and HR-MDS.
The recommended Phase II dose (RP2D) of 250 mg was found to be safe and well-tolerated, achieving RVU120 concentrations in the pharmacologically active range, with a level of target inhibition between 50% and 70%. This level of target inhibition is expected to result in therapeutic efficacy in selected patients or in combinations with synergistic therapies.
RVU120 is emerging as a potential candidate in the first-line treatment of AML, supported by its activity against leukemic stem cells.
RVU120 acts synergistically with venetoclax in both sensitive and venetoclax-resistant models.
At the ENA conference in October 2023, Ryvu presented preclinical data for PRMT5 and the synthetic lethality platform, and Ryvu’s partner – Menarini Group, presented preclinical data for MEN1703 in advanced diffuse large B-cell lymphoma (DLBCL).

Ryvu has developed potentially best-in-class MTA-cooperative PRMT5 inhibitors with outstanding drug-like physicochemical properties and the ability to block methyltransferase activity of PRMT5 with nanomolar concentrations and bioavailable upon oral administration. The novel, optimized inhibitors exhibit a significantly improved pharmacokinetic profile. In addition, the compounds show antitumor efficacy and target engagement in vivo, providing a solid foundation for further development towards clinical trials.
MEN1703 (SEL24) has shown promising antitumor activity in translational studies in various types of DLBCL. These data justify the development of MEN1703 in Phase II clinical trials in this indication.
Expansion of MEN1703 (SEL24) development by Ryvu’s partner – Menarini Group, to include a new Phase II clinical trial in DLBCL.

In September 2023, Ryvu announced the Menarini Group’s decision to expand the development of MEN1703 (SEL24) by initiating a new Phase II clinical trial in patients with DLBCL.

A Phase II study in DLBCL is scheduled to begin in mid-2024. The goal is to evaluate the activity of MEN1703 (SEL24) as monotherapy and in combination with standard therapy in patients with DLBCL.
The study will be initiated based on the potent activity of MEN1703 (SEL24) observed in preclinical lymphoma models. Clinical trials have confirmed the acceptable safety profile and early signs of activity of MEN1703 (SEL24) as a monotherapy. Based on the available data, further program development will continue in patients with DLBCL and potentially in additional indications.
Recent financial events

On February 3, 2024, Ryvu received notice that the second financial milestone was achieved under the collaboration agreement with Exelixis, resulting in a $2M payment to Ryvu. Ryvu and Exelixis are working under a research collaboration and license agreement to develop antibody-drug conjugates (ADCs) with Ryvu’s portfolio of STING agonists.
On March 5, 2024, Ryvu received notice from the European Investment Bank (EIB) that it had met the conditions for disbursement of the first venture debt tranche of €8M. These funds are not yet included in the cash balance reported in this press release, but Ryvu expects to receive the funds on March 13, 2024. As part of the agreement announced in August 2022, Ryvu still has access to an additional €14M in venture debt from the EIB.
UPCOMING EVENTS

Ryvu will attend the AACR (Free AACR Whitepaper) Annual Meeting (San Diego, USA) from April 5-10, 2024, to present preclinical data from its synthetic lethality pipeline, RVU120, and MEN1703 (SEL24).
2023 Fiscal Year Financial Update[1]

Cash Position – On December 31, 2023, Ryvu Therapeutics held $63.7M in cash, cash equivalents, and bonds, compared to $23.2M at the end of 2022. On March 7, 2024, Ryvu Therapeutics held $57.2M in cash, cash equivalents, and bonds, which excludes €8M in venture debt from the EIB to be received imminently.

Operating Revenues – In 2023, Ryvu recognized total operating revenues (including grants) of $16.3M, compared to 2022, when the total operating revenue amounted to $15.8M.

Operating costs, excluding the non-cash cost of valuation of the Incentive Program ($2.0M) and valuation of NodThera shares ($0.9M) in the full year 2023, amounted to $37.6M, representing an increase compared to $26.4M in the previous year.

Net Loss Attributable to Common Shareholders – In 2023, the net loss attributable to common shareholders, excluding the non-cash cost of valuation of the Incentive Program, amounted to $20.0M, compared to $13.8M in the previous year.