On January 9, 2023 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported its program updates and announced upcoming key milestones (Press release, ORIC Pharmaceuticals, JAN 9, 2023, View Source [SID1234626091]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In 2022, we made significant progress across our clinical pipeline, advanced multiple preclinical discovery programs, and further strengthened the balance sheet," said Jacob M. Chacko, MD, chief executive officer. "All three clinical programs commenced dosing last year, have demonstrated good oral bioavailability and dose proportional increases in exposure across multiple cohorts, and are steadily advancing in dose escalation without reaching MTD as we expand clinical trial sites globally. Furthermore, with the recent equity investment by Pfizer we have extended our cash runway into 2025, giving us flexibility to frontload Project Optimus-related dose optimization before selecting final RP2D for all three programs, and we expect to report initial clinical data for ORIC-533, ORIC-114, and ORIC-944 in the second half of 2023."

Updates and Milestones

ORIC-533: a highly potent, orally bioavailable CD73 Inhibitor

Initiated dosing patients in a Phase 1b trial with ORIC-533 as a single agent in relapsed/refractory multiple myeloma in first quarter of 2022.
Presented preclinical data supporting the potential of ORIC-533 in multiple myeloma at AACR (Free AACR Whitepaper) in the second quarter of 2022 and at ASH (Free ASH Whitepaper) in fourth quarter of 2022.
Established a clinical development collaboration with Pfizer in the fourth quarter of 2022 for a potential Phase 2 combination study of ORIC-533 and elranatamab, Pfizer’s investigational B-cell maturation antigen (BCMA) CD3 targeted bispecific antibody.
Filed and received clearance for a Clinical Trial Application (CTA) for ORIC-533 by the Canadian regulatory authority.
Expect to report initial Phase 1b data for ORIC-533 in second half of 2023.

ORIC-114: a brain penetrant, orally bioavailable, irreversible EGFR/HER2 Inhibitor

Initiated dosing patients in a Phase 1b trial with ORIC-114 as a single agent in advanced solid tumors with EGFR or HER2 exon 20 alterations or HER2 amplification in the first quarter of 2022 in South Korea and Australia.
Presented compelling brain exposure and antitumor activity of ORIC-114 in preclinical NSCLC EGFR exon 20 intracranial models at AACR (Free AACR Whitepaper) in the second quarter of 2022.
Filed and received clearance for an IND for ORIC-114 by the US FDA in the third quarter of 2022, and initiated the first US site in the fourth quarter of 2022.
Expect to report initial Phase 1b data for ORIC-114 in second half of 2023.

ORIC-944: a potent and selective allosteric inhibitor of PRC2

Initiated dosing patients in a Phase 1b trial with ORIC-944 as a single agent in prostate cancer in second quarter of 2022.
Ongoing preclinical evaluation of combinations in prostate cancer and other potential indications.
Expect to report initial Phase 1b data for ORIC-944 in second half of 2023.

Discovery Pipeline:

The company advanced multiple targets in small molecule lead optimization, including inhibitors of polo-like kinase 4 (PLK4), which confers synthetic lethality in breast cancers with TRIM37 amplification/elevation. A novel, potent, selective, orally bioavailable PLK4 inhibitor was selected as a development candidate in the fourth quarter of 2022.

Anticipated Program Milestones

ORIC anticipates the following upcoming milestones:

ORIC-533: Report initial safety, PK/PD, and preliminary antitumor activity data from ongoing single agent Phase 1b study in patients with multiple myeloma in the second half of 2023.
ORIC-114: Report initial safety, PK/PD, and preliminary antitumor activity data from ongoing single agent Phase 1b study in patients with EGFR/HER2-mutated cancers in the second half of 2023.
ORIC-944: Report initial safety, PK/PD, and preliminary antitumor activity data from ongoing single agent Phase 1b study in patients with prostate cancer in the second half of 2023.
Corporate Update and Financial Guidance
Concurrent with the clinical development collaboration with Pfizer for ORIC-533, Pfizer purchased $25 million of ORIC common stock in a registered direct offering. As of December 31, 2022, cash, cash equivalents and investments totaled approximately $228 million, which the company expects will be sufficient to fund its operating plan into first half of 2025.

Presentation and Webcast

Jacob M. Chacko, M.D., president and chief executive officer, will present a company overview at the 41st Annual J.P. Morgan Healthcare Conference on Tuesday, January 10, 2022, at 11:15 a.m. PT. A live webcast will be available through the investor section of the company’s website at View Source A replay of the webcast will be available for 90 days following the event.

On January 9, 2023 Prelude therapeutics presented its corporate presentation (Presentation, Prelude Therapeutics, JAN 9, 2023, View Source [SID1234626090]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On January 9, 2023 Nurix therapeutics presented its investor presentation (Presentation, Nurix Therapeutics, JAN 9, 2023, View Source [SID1234626089]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On January 9, 2023 Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported that Robert E. Hoffman, President and CEO of Kintara, will be presenting at the Biotech Showcase Conference in San Francisco.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Biotech Showcase Conference will feature presentations by approximately 400 companies who will be discussing their product pipelines, technologies, services, and products.

Kintara’s webcast will be held on January 10, 2023 at 11:30 am PST.

Registered attendees may attend the presentation in-person or view it via webcast through the Biotech Showcase platform.

On January 9, 2023 – Neurocrine Biosciences, Inc. (NASDAQ: NBIX) and Voyager Therapeutics, Inc. (Nasdaq: VYGR) reported the formation of a new strategic collaboration to advance multiple gene therapies for the treatment of neurological diseases (Press release, Neurocrine Biosciences, JAN 9, 2023, View Source [SID1234626087]). The collaboration includes Voyager’s preclinical, intravenously administered GBA1 gene therapy program for Parkinson’s disease and other GBA1-mediated diseases, which combines a GBA1 gene replacement payload with novel capsids from Voyager’s TRACERTM (Tropism Redirection of AAV by Cell-type-specific Expression of RNA) platform. In addition, Neurocrine Biosciences and Voyager have agreed to collaborate on three new gene therapy programs directed to rare CNS targets, each also leveraging Voyager’s novel TRACER capsids. The collaboration builds upon the long-standing strategic partnership between Neurocrine Biosciences and Voyager and continues to combine Voyager’s expertise in novel capsid discovery, payload design, and neuropharmacology with Neurocrine Biosciences’ expertise in neuroscience and the clinical and commercial development of therapies for patients suffering from serious neurological diseases.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Voyager will host a company conference call and webcast to discuss the collaboration. Full webcast details are provided below.

"This new collaboration with Voyager encompassing GBA1-mediated diseases such as Parkinson’s disease and Gaucher’s disease complements our existing collaboration around Friedreich’s Ataxia and other CNS targets, establishing the foundation for a strong franchise of next-generation gene therapies utilizing Voyager’s TRACER capsids to treat serious neurological diseases," said Jude Onyia, Ph.D., Chief Scientific Officer of Neurocrine Biosciences. "We believe GBA1 gene therapy has the potential to play a transformational role in the future treatment of Parkinson’s disease and other serious neurological diseases."

"This collaboration illustrates the value-creation opportunity presented by combining Voyager’s novel TRACER capsid platform with our deep knowledge of neuropharmacology and payloads to advance next-generation gene therapies for CNS diseases," said Alfred W. Sandrock, Jr., M.D., Ph.D., Chief Executive Officer of Voyager. "We look forward to expanding our engagement with Neurocrine Biosciences, with whom we already enjoy a strong relationship. We anticipate that the opportunities enabled by this collaboration will allow us to continue to invest in our platform and pipeline programs, as well as to advance cutting-edge research initiatives."

Collaboration Details and Financial Terms

Under the terms of the agreement, Neurocrine Biosciences has agreed to pay Voyager $175 million up front, of which Neurocrine Biosciences has agreed to pay approximately $136 million in cash and to purchase approximately $39 million of newly issued equity in Voyager at a price of $8.88 per share, which represents a 50% premium to the average daily volume-weighted average price of Voyager’s stock over the 30 trading days prior to the execution of the transaction. In addition, Neurocrine Biosciences has agreed to fund all costs incurred under the collaboration, subject to the cost- and profit-sharing option terms below.

Regarding the GBA1 gene therapy program, Neurocrine Biosciences has agreed to fund development through the completion of a first Phase 1 trial. Following the data readout from such trial, Voyager has the right, but not the obligation, to elect to co-develop and co-commercialize the GBA1 program with Neurocrine Biosciences in the U.S. under a 50/50 cost- and profit-sharing arrangement in lieu of receiving further U.S. milestone-based payments and royalties or alternatively be eligible for U.S.-based development, regulatory, and commercial milestone payments and tiered royalties, with Neurocrine Biosciences maintaining responsibility for all development and commercialization expenses. If Voyager declines its option for cost and profit sharing on the GBA1 program, under the terms of the collaboration agreement, Voyager will be eligible for up to $985 million in total development milestone payments plus substantial potential commercial milestone payments, and tiered royalties ranging from low double-digit to twenty percent on U.S. net sales. Irrespective of Voyager’s election on its cost- and profit-sharing option, Voyager shall be eligible for potential ex-U.S.-based regulatory and commercial milestone payments, as well as royalties ranging from high-single-digits to mid-teens on ex-U.S. net sales.

Regarding the three new gene therapy programs under the collaboration, Voyager is eligible to earn up to $175 million in development milestone payments plus substantial potential commercial milestone payments for each program, and tiered high single-digit to mid-teens royalties on U.S. net sales and mid-single-digit to low double-digit royalties on ex-U.S. net sales. Neurocrine Biosciences has agreed to fully fund the development of the three new programs.

Neurocrine Biosciences and Voyager have agreed that, following the completion of the transaction, Jude Onyia, Ph.D., Chief Scientific Officer at Neurocrine Biosciences, will join Voyager’s Board of Directors.
The effectiveness of the collaboration agreement and the closing of the sale and issuance of Voyager common stock described above are subject to certain conditions including the expiration or termination of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended, and other customary closing conditions.

Conference Call Details
Voyager will host a conference call and webcast today at 8:45 a.m. ET to discuss the collaboration with Neurocrine Biosciences and early research initiatives. To participate via telephone and join the call live, please register in advance here: https://register.vevent.com/register/BI0a2d1fa796644be08876e1f7b98034d4. Upon registration, telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number and a unique passcode. A live webcast of the call will also be available on the Investors section of the Voyager website, at ir.voyagertherapeutics.com. A replay of the call will be available at the same link approximately two hours after the call’s completion. The replay will be available for at least 30 days following the conclusion of the call.

About the GBA1 Gene Therapy Program

GBA1 is the gene encoding the lysosomal enzyme glucocerebrosidase, and mutations in this gene have been associated with multiple diseases. Up to 10% of Parkinson’s disease patients have a mutation in GBA1, the most common genetic risk factor, increasing the risk of the disease approximately 20-fold. When homozygous, pathologic variants in GBA1 cause the lysosomal disorder, Gaucher disease. AAV-based gene replacement therapies using a blood-brain barrier (BBB)-crossing capsid have the potential to achieve sustained correction of such disorders affecting the central nervous system. In a GBA loss-of-function preclinical model, Voyager has demonstrated CNS target engagement using its intravenous CNS-tropic capsids and delivery of therapeutically relevant levels of the enzyme GCase, which is encoded by GBA1.

About the TRACER AAV Capsid Discovery Platform
Voyager’s TRACER (Tropism Redirection of AAV by Cell-type-specific Expression of RNA) capsid discovery platform is a broadly applicable, RNA-based screening platform that enables rapid discovery of AAV capsids with robust penetration of the blood-brain barrier and enhanced central nervous system (CNS) tropism in multiple species, including non-human primates (NHPs). TRACER generated capsids have demonstrated superior and widespread gene expression in the CNS compared to conventional AAV capsids as well as cell- and tissue-specific transduction, including to areas of the brain that have been traditionally difficult to reach. Separate results have demonstrated the enhanced ability of certain capsids to target cardiac muscle and to de-target the dorsal root ganglia. Voyager is expanding its library of AAV capsids optimized to deliver diverse therapeutic payloads to address a broad range of CNS and other diseases. As part of its external partnership strategy, Voyager has established multiple collaboration agreements providing access to its next-generation TRACER capsids to potentially enable its partners’ gene therapy programs to treat a variety of diseases.