On January 5, 2024 Orion Corporation ("Orion") and MSD (known as Merck & Co., Inc., Rahway, N.J., USA in the United States and Canada) reported to have initiated two pivotal Phase 3 clinical trials evaluating ODM-208/MK5684, an investigational CYP11A1 inhibitor, in combination with hormone replacement therapy (HRT), for the treatment of certain patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Orion, JAN 5, 2024, View Source [SID1234639025]). Patients are now enrolling in the trials, named OMAHA1 (NCT06136624) and OMAHA2a (NCT06136650).

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"The start of our co-development Phase 3 program with MSD provides exciting opportunities to evaluate the potential of ODM-208/MK5684 as a novel treatment of mCRPC, both in front-line and late-line patients, including those with and without androgen receptor ligand binding domain (AR LBD) mutations," said Professor Outi Vaarala, Senior Vice President, Innovative Medicines and Research and Development, Orion. "Our ultimate aim is to bring innovative medicines to all patients with unmet need, and we look forward to the beginning of these studies with our partner, MSD."

"By inhibiting CYP11A1 enzyme activity, we believe ODM-208/MK5684 represents a compelling approach to suppress the production of steroid hormones, a key driver of prostate cancer," said Dr. Scot Ebbinghaus, Vice President, global clinical development, MSD Research Laboratories. "The initiation of these two Phase 3 trials of ODM-208/MK5684 in different stages of mCRPC, in collaboration with Orion, demonstrates our continued commitment to exploring innovative new approaches and pathways to treat this complex disease."

OMAHA1 is a randomized, open-label Phase 3 trial evaluating ODM-208/MK5684 in combination with HRT for the treatment of patients with later-line mCRPC who have failed one prior new hormonal agent (NHA) and one or two prior taxane-based chemotherapies compared to an alternative NHA (abiraterone or enzalutamide). The trial will enroll an estimated 1,200 patients around the world. The primary endpoints are overall survival (OS) and radiographic progression-free survival (rPFS) by AR LBD mutation status. Secondary endpoints include time to first subsequent therapy (TFST), objective response rate (ORR) and duration of response (DOR).

OMAHA2a is a randomized, open-label Phase 3 trial evaluating ODM-208/MK5684 in combination with HRT for the treatment of patients with front-line mCRPC who have failed one prior NHA compared to physician’s choice of NHA (abiraterone or enzalutamide). The trial will enroll an estimated 1,500 patients around the world. The primary endpoints are OS and rPFS by AR LBD mutation status. Secondary endpoints include TFST, ORR and DOR.

About ODM-208/MK-5684

ODM-208/MK5684 is an oral, non-steroidal and selective inhibitor of the CYP11A1 enzyme discovered and developed by Orion and is being investigated for the treatment of hormone-dependent cancers, such as prostate cancer. By inhibiting CYP11A1 enzyme activity, ODM-208/MK5684 is designed to suppress the production of all steroid hormones and their precursors that may activate the androgen receptor signaling pathway.

About metastatic castration-resistant prostate cancer

Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone. In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body, despite the use of androgen-deprivation therapy to block the action of male sex hormones. Approximately 10-20% of patients with prostate cancer are estimated to develop castration-resistant prostate cancer (CRPC) within five years, with at least 84% of these patients presenting with metastases at the time of CRPC diagnosis. Of patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years. mCRPC is associated with a significant mortality rate.

On January 5, 2024 BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) reported preliminary, unaudited ORLADEYO (berotralstat) net revenue for the fourth quarter and full year 2023 (Press release, BioCryst Pharmaceuticals, JAN 5, 2024, View Source [SID1234639024]). The company also provided guidance for full year 2024 ORLADEYO net revenue, full year 2024 operating expenses, expected peak ORLADEYO sales and an accelerated path to profitability.

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"After three years on the market, ORLADEYO continues on a steady growth trajectory to achieve $1 billion at peak. This commercial success, alongside our proven discovery platform that is producing additional first-in-class or best-in-class molecules, uniquely positions BioCryst to achieve financial independence from the capital markets and accelerate our path to profitability," said Jon Stonehouse, president and chief executive officer of BioCryst.

The company also announced that, if its ongoing proof-of-concept trial produces best-in-class data, it plans to out-license late-stage development and commercialization of BCX10013, its potential once-daily, oral Factor D inhibitor, to a partner that can drive the speed and breadth of investment required to accelerate BCX10013 for patients across multiple complement-mediated diseases and maximize the commercial potential of the program. As a result, the company has reduced the size of its R&D organization and accelerated its timeline to profitability.

Preliminary Fourth Quarter and Full Year 2023 ORLADEYO Revenue and 2024 ORLADEYO Outlook
Preliminary, unaudited ORLADEYO net revenue in the fourth quarter of 2023 was $89.9 million (+27 percent y-o-y). Preliminary, unaudited ORLADEYO net revenue for full year 2023 was $325 million (+29 percent y-o-y).

The company expects full year 2024 global net ORLADEYO revenue to be between $380 million and $400 million. The general pattern of revenue throughout 2024 is expected to be similar to past years, with the seasonal impact of prescription reauthorizations and the potential impact of the Inflation Reduction Act in the first quarter driving a quarter-over-quarter revenue decline in the first quarter, followed by a strong return to growth in the second quarter.

"ORLADEYO growth remained strong in the fourth quarter of 2023 as hereditary angioedema patients gain the excellent attack control they expect. Comparing U.S. patient trends year over year (y-o-y), we had more new patient prescriptions and a lower average rate of monthly discontinuations in 2023 compared to 2022. U.S. performance combined with continued global expansion keep ORLADEYO on track for $1 billion in peak sales," said Charlie Gayer, chief commercial officer of BioCryst.

Operating Expense and Profitability Outlook
The company expects full year 2024 operating expenses to be between $365 million and $375 million, flat to expected full year 2023 operating expenses. The company now expects that R&D expenses in 2024 will be reduced by $20 million versus 2023. This represents a $45 million to $55 million reduction from the 2024 R&D expense guidance it provided at its R&D Day in November 2023, and reflects both the R&D restructuring and the postponement of previously planned capital expenditures at its Discovery Center in Alabama. SG&A expenses are expected to increase by $20 million in 2024, primarily to support the continued U.S. and global growth of ORLADEYO to $1 billion in peak sales.

This operating expense outlook does not reflect non-cash stock compensation expense, or one-time expenses related to the reduction of 59 jobs (10 percent of total organization) in the first quarter of 2024.

Based on the company’s disciplined approach to capital allocation, and the revenue expected from ORLADEYO, the company expects to achieve a full-year operating profit in 2024 (not including non-cash stock compensation), be approaching quarterly positive earnings per share (EPS) and positive cash flow in the second half of 2025 (not including non-cash stock compensation), and be profitable on an EPS basis, with positive cash flow, for full year 2026. The company expects it can achieve these financial milestones without raising additional funds and does not intend to draw the additional $150 million of debt available to it from Pharmakon.

Presentation Tuesday at 42nd Annual J.P. Morgan Healthcare Conference
On Tuesday, January 9, 2024 at 6:00 p.m. ET, the company will present at the 42nd Annual J.P. Morgan Healthcare Conference in San Francisco. Links to a live audio webcast and replay of the presentation may be accessed in the Investors section of BioCryst’s website at https://www.biocryst.com/.

On January 5, 2024 Vor Biopharma presented its corporate presentation (Presentation, Vor BioPharma, JAN 5, 2024, View Source [SID1234639023]).

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On January 5, 2024 TG Therapeutics, Inc. (NASDAQ: TGTX), reported that Michael S. Weiss, the Company’s Chairman and Chief Executive Officer, will present at the 42nd Annual J.P. Morgan Healthcare Conference. The presentation is scheduled to take place on Tuesday, January 9, 2024, at 4:30 PM PT (Press release, TG Therapeutics, JAN 5, 2024, View Source [SID1234639022]).

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A live webcast of this presentation will be available on the Events page, located within the Investors & Media section, of the Company’s website at View Source A replay of the webcast will be available on TG’s website following the event.

On January 5, 2024 Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on changing the possible for patients through engineered cells, reported the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application to initiate a study of SC262 in patients with relapsed or refractory B-cell malignancies, initially in patients who have received prior CD19-directed CAR T therapy (Press release, Sana Biotechnology, JAN 5, 2024, View Source [SID1234639020]).

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Engineered CAR T cell therapies for B-cell malignancies use binders to target proteins expressed on the surface of B cells. One such protein, CD19, has been the target of all approved autologous CAR T therapies for B-cell lymphoma and B-cell acute lymphoblastic leukemia to date. Unfortunately, incomplete responses or relapses occur in approximately 60% of CD19 CAR T-treated patients. CD22, which is also a B-cell surface protein, has emerged as an alternative to address failure to achieve durable complete responses with CD19-directed CAR T therapy. SC262 expresses the same CAR, including the same CD22 binder, used in CD22-directed CAR T therapies tested in multiple academic clinical trials. To date, these trials have shown durable complete responses in a substantial number of patients in the relapse setting following treatment with a CD19-directed CAR T therapy.

"Patients who have failed a CD19-directed CAR T therapy represent a significant unmet need, and this population is growing as more patients receive these therapies," said Doug Williams, PhD, Sana’s President of Research and Development. "SC262 represents an important potential option for these patients and is the next step in building Sana’s hypoimmune CAR T therapy platform. Over the past twelve months, Sana has received three IND regulatory clearances, as well as supported the authorization of an investigator-sponsored CTA, to begin new studies utilizing our hypoimmune platform in seven different indications in oncology, B-cell mediated autoimmune diseases, and type 1 diabetes. We look forward to presenting data from all of these studies this year, including initial proof of concept data for SC262 later this year."

About SC262 in B-cell Malignancies
SC262 is a hypoimmune, CD22-directed allogeneic CAR T cell therapy derived from healthy donor CD4+ and CD8+ T cells. SC262 is developed with Sana’s hypoimmune platform, which is designed to overcome the immunologic rejection of allogeneic cells and may result in longer CAR T cell persistence and a higher rate of durable complete responses for patients with B-cell malignancies. CD22 is expressed on lymphoma and leukemia cells in most patients with these diseases, including those that have failed CD19- and/or a CD20-directed therapies. SC262 is initially being explored in patients that have failed a previous CD19-directed therapy. The hypoimmune technology includes disruption of major histocompatibility (MHC) class I and MHC class II expression to allow cells to evade the adaptive immune system, which includes antibody and T cell responses, as well as overexpression of CD47 to evade the innate immune cell system, in particular macrophages and natural killer (NK) cells. The company has presented data across multiple preclinical models highlighting the potential of this platform to cloak cells from immune recognition and the potential of SC262 as a therapeutic for patients with B-cell malignancies.

About Hypoimmune Platform
Sana’s hypoimmune platform is designed to create cells ex vivo that can "hide" from the patient’s immune system to enable the transplant of allogeneic cells without the need for immunosuppression. We are applying the hypoimmune technology to both donor-derived allogeneic T cells, with the goal of making potent and persistent CAR T cells at scale, and pluripotent stem cells, which can then be differentiated into multiple cell types at scale. Preclinical data published in peer-reviewed journals demonstrate across a variety of cell types that these transplanted allogeneic cells are able to evade both the innate and adaptive arms of the immune system while retaining their activity. Our most advanced programs utilizing this platform include an allogeneic CAR T program targeting CD19+ cancers, an allogeneic CAR T program for B-cell mediated autoimmune diseases, an allogeneic CAR T program targeting CD22+ cancers, and stem-cell derived pancreatic islet cells for patients with type 1 diabetes.