• Signed a collaboration agreement with BioNTech to develop and commercialize immunomodulatory small molecule therapeutics; deal terms included €20M upfront payment, €20M equity investment in Ryvu, research funding, and downstream milestones and royalties;
• Successfully completed a Public Offering, raising gross proceeds of $56M;
• Planning to advance RVU120 to Phase II in the treatment of solid tumors and AML/HR-MDS in 2Q and 2H 2023 respectively; clinical updates at upcoming major medical meetings;
• Presenting updated in vivo data from the MTA-cooperative PRMT5 inhibitor program at the AACR Annual Meeting 2023;
• Strengthened cash position of $72.5 million (as of March 17, 2023) extends runway to 2025;

Krakow, Poland – March 24, 2023 – Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, today reported financial results for the fourth quarter and the full year ended December 31, 2022, and provided a corporate update.

“2022 was a highly productive year for Ryvu as we made significant strides across our clinical programs, collaboration activity, and in strengthening our balance sheet,” said Pawel Przewiezlikowski, co-founder, largest shareholder and CEO of Ryvu Therapeutics. “During the second half of 2022, we secured over $110 million in proceeds from two successful licensing agreements with Exelixis and BioNTech, a secondary offering on the Warsaw Stock Exchange, and a venture debt agreement with the European Investment Bank. We now enter 2023 well-positioned to execute our goals with the priority on advancing RVU120 to Phase II studies in solid tumors and AML/MDS. We look forward to readouts and updates across our clinical and preclinical programs throughout the year, including data for the MTA-cooperative PRMT5 inhibitors at the upcoming AACR Annual Meeting 2023.”

FOURTH QUARTER 2022 AND RECENT HIGHLIGHTS

$56M Secondary Offering

In December, Ryvu completed its public offering of 4,764,674 Series J common shares (“Public Offering”) on the Warsaw Stock Exchange resulting in gross proceeds of $56M (250.3M PLN) from institutional (including the largest Polish pension and investment funds), individual, and industry investors including the Leukemia & Lymphoma Society and BioNTech, which became an 8% shareholder in Ryvu. Among the investors participating in this offering were also company insiders (including the CEO) with a total investment of over $5M in the offering. The transaction was the largest-ever capital-raising transaction by a Polish biotechnology company.

Global Collaboration Agreement with BioNTech

BioNTech and Ryvu entered a multi-target research collaboration to develop multiple small molecule programs targeting immune modulation in cancer and potentially other disease areas based on targets selected by BioNTech. Additionally, BioNTech received a global, exclusive license to develop and commercialize Ryvu’s STING agonist portfolio as standalone small molecules. Under the terms of the agreement, BioNTech paid Ryvu an upfront fee of €20 million in exchange for certain rights to Ryvu’s STING agonist portfolio as standalone small molecules and for certain rights and options to license multiple small molecule programs as part of a multi-target research collaboration. In addition, BioNTech has committed to making an equity investment of €20 million and providing research funding for immune modulation programs.

RVU120 and SEL24 (MEN1703) data readout at the 2022 American Society of Hematology (ASH) Annual Meeting

RVU120 was well tolerated across all doses and demonstrated single-agent activity with a complete response, 4 blast reductions, and 4 erythroid and/or platelet responses in a first-in-human Phase 1b dose-escalation trial in relapsed/refractory (R/R) acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS).

In addition, the preclinical data of SEL24 (MEN1703) in combination with gilteritinib demonstrated antitumor activity and complete responses in vivo, in multiple myeloma (MM), Hodgkin’s Lymphoma (HL), and Diffuse Large B-Cell Lymphoma (DLBCL) as well as in AML. The study supported the promising therapeutic potential of SEL24 (MEN1703) in MM and the underlying mechanism of PIM inhibition.

Ryvu plans to advance RVU120 to Phase II in the treatment of solid tumors and AML/HR-MDS in 2Q and 2H 2023 respectively.

Ryvu Therapeutics Named the Stock Exchange Company of the Year

Ryvu was named the Best Company on the Warsaw Stock Exchange (WSE) for 2022 in an annual competition organized by “Puls Biznesu” – one of the largest business daily publications in Poland. Ryvu was also the winner in three other categories: “Investor Relations”, “Development Perspectives”, and “Products and Services Innovation”.

This year marked the 24th edition of the competition, which is the most prestigious ranking in the Polish capital market. A panel of 103 experts (68 analysts and 35 fund managers) graded 140 of the largest firms trading on the WSE (20 from WIG20, 40 from mWIG, and 80 from sWIG) across five categories: management board competencies, success, products and services innovation, investor relations, and development perspectives.

 

Upcoming clinical and corporate milestones

• RVU120
  • Updated data from the RVU120 Phase I study in patients with relapsed/refractory metastatic or advanced solid tumors will be presented in Q2 2023;
  • Updated Phase 1 data in AML and HR-MDS will be presented in Q2 2023;
• SEL24 (MEN1703)
  • Updates from the Phase I/II study of SEL24/MEN1703, a first-in-class dual PIM/FLT3 kinase inhibitor, in patients with IDH1/2-mutated acute myeloid leukemia expected in 2023; further development opportunities currently under consideration by Menarini;
• Synthetic lethality
  • Updated in vivo data for the MTA-cooperative PRMT5 inhibitors will be presented at the upcoming 2023 AACR Annual Meeting in Orlando, Florida;

 

Upcoming conference

• American Association for Cancer Research (AACR) Annual Meeting, taking place April 14 – 19, 2023, in Orlando, Florida

The poster showcases a series of MTA-cooperative PRMT5 inhibitors identified by Ryvu. These compounds have drug-like physicochemical properties, block methyltransferase activity with nanomolar IC50 values, and are orally bioavailable given the drug metabolism and pharmacokinetics profile. It has been demonstrated that these inhibitors selectively inhibit the growth of MTAP-deleted cancer cells in prolonged 3D culture, which correlates with the inhibition of PRMT5-dependent protein symmetric dimethylation (SDMA). Selectivity effects between MTAP deleted and WT cells exceed 100-fold both for SDMA and growth inhibition. Efficacy studies with the lead compound resulted in tumor growth inhibition in a MTAP-deleted model, accompanied by significant inhibition of the target proximal pharmacodynamic biomarker.

• Details on the poster presentation
  • Title: Discovery of novel MTA-cooperative PRMT5 inhibitors as targeted therapeutics for MTAP-deleted cancers
  • Session Title: New Drug Targets
  • Abstract Number: 449
  • Date and Time: Sunday, Apr 16, 2023, 1:30 PM – 5:00 PM
  • Location: Poster Section 16

 

2022-2024 Development Plans

Key development goals for 2022-2024 are divided into three areas:

1. Clinical Development Pipeline:

a. Completing the ongoing Phase I clinical studies of Ryvu’s fully-owned lead asset RVU120 in AML/HR-MDS and solid tumors;

b. Advancing the clinical development of RVU120 as a monotherapy by executing Phase II studies in AML/HR-MDS and selected solid tumors;

c. Expanding the therapeutic potential of RVU120 by initiating Phase I/II clinical development in combination regimens in AML/HR-MDS with synergistic drug partners and in additional hematology indications and solid tumor indications;

d. Supporting the clinical development of the partnered candidate, SEL24 (MEN1703) by Menarini Group;

2. Early Pipeline (Discovery and Preclinical Development):

a. Completing preclinical development and advancing into Phase I clinical trials of one program from Ryvu’s early pipeline;

b. Strengthening Ryvu’s Synthetic Lethality Platform to deliver first-in-class preclinical candidates and further expansion of proprietary target discovery platform;

3. Business:

a. Achieving financial milestones in existing R&D collaborations;

b. Advancing selected programs by partnering with collaborators with synergistic competencies and resources, signing at least one new partnership agreement annually;

Beyond the current cash position of $72.5M (as of March 17, 2023) and the EIB venture debt,  Ryvu aims to secure additional non-dilutive funding from grants and potential milestones in existing collaborations in the upcoming quarters.

 

Fourth Quarter and Full-Year 2022 Financial Update

Cash Position – On December 31, 2022, Ryvu Therapeutics held $23.2M in cash and cash equivalents, compared to $20.5M at the end of 2021. As of March 17, 2023, Ryvu Therapeutics held $72.5M in cash and cash equivalents. The increase is a result of the recent public offering.

Operating costs, excluding the non-cash cost of valuation of the Incentive Program ($5.0M) and valuation of NodThera shares ($2.0M) in full-year 2022 amounted to $26.4M and are related primarily to research and development expenditures, while the operating costs without the Incentive Program ($5.9M) and valuation of NodThera shares ($0.1M – decrease in costs) for the same period last year amounted to $23.7M.

Net Loss Attributable to Common Shareholders – Net loss attributable to common shareholders excluding the non-cash cost of valuation of the Incentive Program was $1.4M, for the fourth quarter of 2022, compared to the $2.6M, for the fourth quarter of 2021. Net loss excluding the non-cash cost of valuation of the Incentive Program for the year ended December 31, 2022, was $13.8M, as compared to a net result of $14.5M for the year ended December 31, 2021.