On January 13, 2025 Foghorn Therapeutics Inc. (Nasdaq: FHTX), a clinical-stage biotechnology company pioneering a new class of medicines that treat serious diseases by correcting abnormal gene expression, reported its strategic objectives for 2025 (Press release, Foghorn Therapeutics, JAN 13, 2025, View Source [SID1234649654]).

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"In 2025, we expect important progress across our inhibitor and degrader programs. Our highly selective SMARCA2 inhibitor, FHD-909, continues to enroll and dose patients in a Phase 1 trial for SMARCA4 mutated cancers, with NSCLC as the primary patient population. In addition, for FHD-909, preclinical combination data with pembrolizumab and KRAS inhibitors will be presented at the AACR (Free AACR Whitepaper) Annual Meeting in April, with partner Lilly," said Adrian Gottschalk, President and Chief Executive Officer of Foghorn. "We are also excited with the progress of our preclinical pipeline. We have successfully achieved selective degradation of ARID1B, a major synthetic lethal target implicated in up to 5% of all solid tumors, and plan to provide a program update in 2025. We are continuing to advance our Selective CBP degrader and our Selective EP300 degrader, which are both implicated in a wide range of cancers. With our strong balance sheet and pipeline programs advancing, we look forward to an impactful 2025."

*Unaudited, estimated as of December 31, 2024

Program Overview and Upcoming Milestones

FHD-909 (LY4050784). FHD-909 is a first-in-class oral SMARCA2 selective inhibitor that has demonstrated in preclinical studies to have high selectivity over its closely related paralog SMARCA4, two proteins that are the catalytic engines across all forms of the BAF complex. Selectively blocking SMARCA2 activity is a promising synthetic lethal strategy intended to induce tumor death while sparing healthy cells. SMARCA4 is mutated in up to 10% of NSCLC alone and implicated in a significant number of solid tumors.
•Advancing Phase 1 trial. First patient dosed in October 2024 in the Phase 1 trial for FHD-909 in SMARCA4 mutated cancers, with NSCLC as the primary target population.
•Preclinical combination data to be presented. In 2025, preclinical data for FHD-909 in combination with pembrolizumab or KRAS inhibitors will be presented at the AACR (Free AACR Whitepaper) Annual Meeting (April 25-30, 2025).

Ongoing strategic collaboration with Lilly. Collaborating with Lilly to create novel oncology medicines that includes a U.S. 50/50 co-development and co-commercialization agreement for Foghorn’s selective SMARCA2 oncology program, agreements for a selective inhibitor and a selective degrader, and an additional undisclosed oncology target. The collaboration also includes three discovery programs from Foghorn’s proprietary Gene Traffic Control platform.

Selective CBP degrader program. Selectively targets CBP in EP300 mutated cancer cells found in many types of cancer, including bladder, gastric and endometrial cancers. CBP and EP300 are highly similar acetyltransferases that create a synthetic lethal relationship when EP300 is mutated. Attempts to selectively drug CBP have been challenging due to the high level of similarity between the two proteins, while dual inhibition of CBP/EP300 has been limited by hematopoietic toxicity.
•Identified potent and selective CBP protein degraders. Pharmacodynamic and pharmacokinetic preclinical data demonstrate:
oDeep and sustained CBP degradation significantly inhibited tumor growth in mouse xenograft solid tumor models.
oRobust monotherapy preclinical anti-tumor activity that was not associated with significant body weight loss, thrombocytopenia or anemia.
oLong-acting injection formulation that resulted in tumor regression from a single dose in a mouse xenograft efficacy study.

Selective EP300 degrader program. Selective degradation of EP300 for the treatment of hematopoietic malignancies and prostate cancer. Attempts to selectively drug EP300 have been challenging due to the high level of similarity between EP300 and CBP, while dual inhibition of CBP/EP300 has been limited by hematopoietic toxicity. EP300 lineage dependencies are established in multiple myeloma, and diffuse large B cell lymphoma.

•Identified potent and selective EP300 degraders and advancing oral degrader efforts. Pharmacodynamic and pharmacokinetic preclinical data demonstrate candidates:
oAre well tolerated in vivo with no observed decrease in platelet levels, and no effects on megakaryocyte viability at pharmacologically relevant concentrations in ex vivo studies.
oHave robust anti-tumor activity in solid tumors and hematological malignancies, including prostate cancer, multiple myeloma, and diffuse large B cell lymphoma.

Selective ARID1B degrader program. Selectively targets and degrades ARID1B in ARID1A-mutated cancers. ARID1A is the most mutated subunit in the BAF complex and amongst the most mutated proteins in cancer. These mutations lead to a dependency on ARID1B in several types of cancer, including ovarian, endometrial, colorectal and bladder. Attempts to selectively drug ARID1B have been challenging because of the high degree of similarity between ARID1A and ARID1B and the fact that ARID1B has no enzymatic activity to target.
•ARID1B is a major synthetic lethal target implicated in up to 5% of all solid tumors.
•Developed highly potent and selective binders. Preclinical data demonstrated potent and selective small molecule binders to ARID1B.
•Selective degradation of ARID1B achieved. Foghorn has successfully selectively degraded ARID1B and expects to provide an update on the Selective ARID1B degrader program in 2025.

Chromatin Biology and Degrader Platform
Foghorn continues to advance its chromatin biology and degrader platform with investments in novel ligases, long-acting injectables, oral delivery and induced proximity.

Strong Balance Sheet and Cash Runway. As of December 31, 2024, the Company had $243.8 million cash, cash equivalents and marketable securities (unaudited), providing cash runway into 2027.

On January 13, 2025 Phio Pharmaceuticals Corp. (Nasdaq: PHIO) is a clinical-stage biotechnology company developing therapeutics that use its INTASYL siRNA gene silencing technology designed to make the body’s immune cells more effective in killing cancer cells (Press release, Phio Pharmaceuticals, JAN 13, 2025, View Source [SID1234649670]). Phio reported pathologic responses for patients enrolled in the 2nd cohort, which includes 2 patients with a complete response or 100% tumor clearance.

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Phio’s ongoing Phase 1b clinical study (NCT 06014086) is designed to evaluate the safety and tolerability of neoadjuvant use of intratumoral PH-762 in Stages 1, 2 and 4 cutaneous squamous cell carcinoma, Stage 4 melanoma and Stage 4 Merkel cell carcinoma.

Of the patients enrolled to date, 6 patients were diagnosed with cutaneous squamous cell carcinoma and 1 patient was diagnosed with metastatic melanoma. At Day 36 (tumor excision), while patients in the first cohort had stable disease, results are now available for the 4 patients who completed treatment in the 2nd cohort:

· Complete response (100% tumor clearance) is reported for 2 patients with cutaneous squamous cell carcinoma. Partial response (90% tumor clearance) is reported for 1 patient with cutaneous squamous cell carcinoma and 1 patient had stable disease, having not progressed.

There have been no dose-limiting toxicities, or clinically relevant treatment-emergent adverse events in the patients receiving intratumoral PH-762. The intratumoral injections have been well tolerated.

"We are pleased and encouraged by the profound tumor response in the second dose cohort, coupled with reassuring safety data," said Mary Spellman MD, Phio’s acting Chief Medical Officer. "We look forward to continued enrollment which will permit assessment of higher dose concentrations of PH-762."

"These positive results in the early stages of dose escalation offer promise for our vision, ‘striving for a cancer free future’ using INTASYL technology" said Robert Bitterman, CEO of Phio Pharmaceuticals.

On January 13, 2025 Ginkgo Bioworks (NYSE: DNA), which is building the leading platform for cell programming and biosecurity, reported a research collaboration with Universal Cells, an Astellas company, to optimize next-generation induced pluripotent stem cell (iPSC)-derived cancer cell therapies (Press release, Ginkgo Bioworks, JAN 13, 2025, View Source [SID1234649686]). This collaboration underscores Ginkgo’s capacity to deploy high-throughput biological approaches to tackle the complex challenge set associated with development of therapies targeting solid tumors.

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iPSC-derived cell therapies have the potential to transform cancer care by offering scalable, ‘off-the-shelf’ treatment options. However, bringing efficacious therapies to patients requires robust design and screening processes to improve persistence in the patient to enable durable clinical responses. By combining Universal Cells’ proprietary iPSC-derived cell technologies with Ginkgo’s expertise in design and screening large CAR libraries and its high throughput, multimodal immune cell engineering platform, the companies aim to accelerate the development of more potent and durable cell therapies while maintaining manufacturability at scale.

Ginkgo’s approach leverages computational tools, deep expertise in library assembly and screening, and rigorous statistical analysis and biological insight to help partners discover and engineer optimal therapeutic designs with greater speed and precision. Ginkgo’s platform capabilities extend across multiple dimensions of cell therapy development, including chimeric antigen receptor (CAR) discovery and optimization, armoring strategies for enhanced cell survival and persistence, and gene editing tools for immune cell engineering. Ginkgo employs high-throughput pooled and arrayed screening methods that enable the simultaneous testing of numerous CAR designs from transcriptome to cell function. This approach facilitates discoveries that aim to improve immune cell persistence and functionality.

"We’re excited to embark on this collaboration, which represents a significant milestone for Ginkgo as we expand our cell therapy portfolio," said Jason Kelly, CEO and co-founder of Ginkgo Bioworks. "Teaming up with Universal Cells, part of Astellas, allows us to bring our comprehensive immune cell engineering capabilities to a highly respected, global pharmaceutical leader. We look forward to working together to optimize iPSC-derived allogeneic cell therapies that have the potential to improve patient outcomes and reshape how we treat solid tumors."

"Cell therapies hold immense promise, but realizing their full potential requires innovation at every step, from design to delivery," said Dr. Narendra Maheshri, VP, Genetic Medicines at Ginkgo Bioworks. "Our platform enables partners to rapidly explore the functional impact of a large number of CAR designs simultaneously, and then iterate to further refine those designs. By applying this approach with Universal Cells, we aim to help accelerate CAR approaches, opening up new possibilities in the fight against cancer."

To learn more about how you can leverage Ginkgo’s capabilities in cell therapy and gene editing – from CAR-T to CRISPR and beyond – please visit our website.

On Jan. 13, 2025 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported highlights for the upcoming company presentation at the 43rd Annual J.P. Morgan Healthcare Conference on Thursday, January 16, 2025 at 9:00 AM PT/12:00 PM ET (Press release, Precigen, JAN 13, 2025, View Source [SID1234649719]). Participants may view details for Precigen’s company presentation at Precigen’s website in the Events & Presentations section at investors.precigen.com/events-presentations.

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"Our recent BLA submission for PRGN-2012 in RRP puts our commercial readiness activities in high gear and we are well underway to ensure full readiness in anticipation of a potential launch in the second half of this year. We have made tremendous progress in the past six months on payer and prescriber analysis, clarifying the market opportunity, building out our commercial and distribution infrastructure, and other activities to ensure we fully coordinate the payor, provider, and patient journeys for launch," said Phil Tennant, Chief Commercial Officer of Precigen. "Our updated analysis of the market using claims data and electronic health records underscores the significant potential for PRGN-2012 in RRP with approximately 27,000 adult patients now identified in the US and we expect more than 125,000 patients ex-US. We are confident that we will be ready to commercialize in the US as soon as we receive approval so that patients can gain access to this game-changing treatment."

"With 100% manufacturing success rate demonstrated to date, we anticipate our in-house commercial drug substance cGMP manufacturing facility will be ready to meet the projected demand to support potential commercial launch in the second half of this year," said Rutul Shah, Chief Operating Officer of Precigen.

"We continue to de-risk our PRGN-2012 asset and now that we have submitted the BLA in RRP, we are a step closer to completing our transition to a commercial-stage company. As we start 2025, we are laser focused on working with the FDA and advancing commercial readiness efforts in anticipation of a potential launch in the second half of this year. In addition, we are preparing for submissions to other health authorities in our prioritized global markets. Beyond RRP, we see immense potential for the AdenoVerse platform in other HPV6/11-driven indications, such as genital warts, and HPV16/18-driven indications, such as cervical cancer and head and neck cancers," said Helen Sabzevari, PhD, President and CEO of Precigen. "As communicated previously, we plan to pursue strategic partnerships to advance our UltraCAR-T programs, which deliver autologous, antigen-specific CAR-T cells overnight to a patient at the patient’s medical center. In conjunction, we are preparing for an end of Phase 1b meeting with the FDA for PRGN-3006 to share results for this highly promising program, including new clinical biomarker data that may further enable patient stratification and positively impact efficacy."

Realizing Precigen’s Commercial Vision for PRGN-2012 AdenoVerse Gene Therapy in RRP

PRGN-2012 (INN: zopapogene imadenovec†) is an investigational off-the-shelf AdenoVerse gene therapy designed to elicit immune responses directed against cells infected with human papillomavirus (HPV) 6 or HPV 11 for the treatment of recurrent respiratory papillomatosis (RRP), a rare and devastating chronic disease for which the current standard-of-care is repeated surgeries. If approved, PRGN-2012 has the potential to be the first US Food and Drug Administration (FDA)-approved therapeutic for the treatment of RRP.
PRGN-2012 received Breakthrough Therapy Designation from the FDA. PRGN-2012 also received Orphan Drug Designation from the FDA and Orphan Drug Designation from the European Commission.
In December 2024, the Company announced that it had completed the submission of a biologics license application (BLA) with a request for priority review for PRGN-2012 for the treatment of adults with RRP to the FDA. The submission is in the initial 60 day review period, during which time the FDA will decide whether to accept the BLA for further review and set the Prescription Drug User Fee Act (PDUFA) action date. The BLA included a request for priority review, which, if granted, would reduce the review timeline from the standard 10-month to a priority 6-month review from the date the submission is accepted by the FDA.
The BLA, under an accelerated approval pathway, is supported by data from the Phase 1/2 pivotal study in which more than 50% of patients achieved Complete Response and more than 85% of patients had a decrease in surgical interventions in the year after PRGN-2012 treatment compared to the year prior to treatment. PRGN-2012 was well-tolerated with no dose-limiting toxicities and no treatment-related adverse events greater than Grade 2.
The confirmatory clinical trial of PRGN-2012 was initiated and is enrolling patients in accordance with the guidance from the FDA to initiate the study prior to submission of the BLA.
The Company continues to rapidly advance its commercial and manufacturing readiness campaign in anticipation of a potential 2025 launch.
Maximizing the Potential of PRGN-2009 AdenoVerse Gene Therapy in HPV-associated Cancers

PRGN-2009 Phase 2 clinical trials under a cost-effective cooperative research and development agreement (CRADA) with the National Cancer Institute (NCI) in recurrent/metastatic cervical cancer and in newly diagnosed HPV-associated oropharyngeal cancer are ongoing.
Enrollment was paused in the cervical cancer Phase 2 clinical trial at non-NCI sites as part of strategic reprioritization activities in 2024.
Maximizing the Value of the UltraCAR-T Platform through Strategic Partnerships

Enrollment was completed for the Phase 1b trial for PRGN-3006, which received Fast Track designation from the FDA for the treatment of relapsed or refractory (r/r) acute myeloid leukemia (AML).
Based on the results of correlative studies of the patient samples from the Phase 1/1b study, the Company has identified clinical biomarkers that correlate to objective responses after PRGN-3006 treatment in r/r AML patients. This advancement may further enable patient stratification and positively impact efficacy.
The Company is preparing for an end of Phase 1b meeting with the FDA to discuss results and next steps.
The Company plans to focus on strategic partnership opportunities to advance this promising UltraCAR-T program in AML.
*Cash on-hand is preliminary and unaudited and reflects preliminary financial information as of December 31, 2024. In preparing this information, the Company’s actual financial position as of December 31, 2024 has not yet been finalized by management or reviewed or audited by the Company’s independent registered public accounting firm. This information is also not a comprehensive statement of financial position or results of operations as of or for the year-ended December 31, 2024. Subsequent information or events may lead to material differences between the foregoing preliminary financial information and those reported in the Company’s subsequent SEC filings. Accordingly, investors should not place undue reliance on this preliminary financial information.

†zopapogene imadenovec is the international nonproprietary name (INN) for the investigational therapeutic known as PRGN-2012. Zopapogene imadenovec has not been approved by any health authority in any country for any indication.

On January 13, 2025 Autolus therapeutics presented its corporate presentation (Presentation, Autolus, JAN 13, 2025, View Source [SID1234649639]).

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