On March 19, 2025 TwoStep Therapeutics, a biotechnology company developing innovative, first-in-class, multispecific targeted peptide conjugate therapies for solid tumors, reported its debut public scientific presentation on March 27, 2025, at the 4th Novel Conjugates Summit taking place in Boston, Massachusetts (Press release, TwoStep Therapeutics, MAR 19, 2025, View Source [SID1234651276]). This presentation will highlight the outstanding preclinical efficacy and safety of its lead tumor-targeted drug conjugate program, along with a first look at their new radiopharmaceutical program.

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Oral Presentation:
Title: Overcoming Tumor Heterogeneity via Multispecific Targeting
Date and Time: Thursday, March 27, 2025, at 9:00 a.m. ET
Invited Speaker: Caitlyn Miller, PhD, Co-Founder & CEO of TwoStep Therapeutics

TwoStep Therapeutics is a Stanford University spin-out launched in 2024, co-founded by Nobel Prize winner Carolyn Bertozzi, Jennifer Cochran, Ron Levy, and Caitlyn Miller, with seed investment of $8.7M to date.

"The company has made tremendous progress since our launch, and we’re excited to share our advancements at this summit," said Caitlyn Miller, CEO of TwoStep Therapeutics. "This event provides an excellent opportunity to highlight our innovative research and explore potential partnerships to further our mission of developing effective cancer therapies."

On March 19, 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 full year 2024 financial results and business updates (Press release, Precigen, MAR 19, 2025, View Source [SID1234651260]).

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"Last year, we achieved several milestones on our path to potentially bring our innovative PRGN-2012 therapy to RRP patients, including presentation of groundbreaking pivotal data and BLA submission to the FDA. Through prioritizing our portfolio and financing activities, we strengthened our financial position, enabling ongoing commercial and manufacturing readiness efforts for PRGN-2012 in anticipation of a potential 2025 launch. Our commercial organization has been working to scale up quickly, right-sizing the organization to rapidly capitalize on the immense demand from patients and treating physicians for a new treatment paradigm that may finally address the underlying cause of the disease," said Helen Sabzevari, PhD, President and CEO of Precigen. "Already this year, our BLA for PRGN-2012 received priority review from the FDA with an August 2025 PDUFA action date, bringing us a step closer to launching the first and only FDA-approved treatment to the approximately 27,000 adult RRP patients in the US. FDA approval for PRGN-2012 would fundamentally change Precigen, enabling the transition from clinical to commercial stage with the real and imminent potential to begin realizing product sales this year and providing financial tailwinds to enable potential expansion of PRGN-2012 to new indications and geographical markets."

"As a result of the preferred stock offering and sale of intellectual property and related royalty rights for a non-core asset, we extended our cash runway into 2026, beyond the potential commercial launch of PRGN-2012 this year. We are preparing for the transition to a commercial stage company and the potential to add product-related revenue," said Harry Thomasian Jr., CFO of Precigen.

Key Program Highlights

PRGN-2012 (nonproprietary name: zopapogene imadenovec†) AdenoVerse Gene Therapy in RRP

PRGN-2012 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). PRGN-2012 received Breakthrough Therapy Designation, Orphan Drug Designation, and an accelerated approval pathway from the FDA, and Orphan Drug Designation from the European Commission.

· In February 2025, the US Food and Drug Administration (FDA) accepted the company’s biologics license application (BLA) for PRGN-2012, and granted priority review to the BLA with a Prescription Drug User Fee Act (PDUFA) target action date set for August 27, 2025. The FDA has indicated that they are not currently planning to hold an advisory committee meeting to discuss the BLA.

· Results from the pivotal clinical study of PRGN-2012 for the treatment of RRP were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in a late-breaking oral presentation titled, "PRGN-2012, a novel gorilla adenovirus-based immunotherapy, provides the first treatment that leads to complete and durable responses in recurrent respiratory papillomatosis patients" and published in The Lancet Respiratory Medicine.

· Pivotal study successfully met its primary safety and pre-specified primary efficacy endpoints.

· PRGN-2012 was well-tolerated with no dose-limiting toxicities and no treatment-related adverse events greater than Grade 2.

· 51% (18 out of 35) of patients achieved Complete Response, requiring no surgeries after treatment with PRGN-2012. Complete Responses have been durable beyond 12 months with median duration of follow up
of 24 months, with some complete responders surgery-free beyond three years as of the August 28, 2024 data cutoff.

· 86% of patients (30 out of 35) had a decrease in surgical interventions in the year after PRGN-2012 treatment compared to the year prior to treatment; RRP surgeries reduced from a median of 4 (range: 3-10) pre-treatment to 0 (range: 0-7) post-treatment.

· PRGN-2012 treatment induced HPV 6/11-specific T cell responses in RRP patients with a significantly greater expansion of peripheral HPV-specific T cells in responders compared with non-responders.

· PRGN-2012 significantly (p < 0.0001) improved anatomical Derkay scores and VHI-10 scores in complete responders.

· Patient enrollment continues to advance in the confirmatory clinical trial of PRGN-2012 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 launch in 2025.

· Based on recently updated internal analysis derived from review of claims data, the market opportunity for PRGN-2012 in RRP is estimated to be approximately 27,000 adult patients in the US and more than 125,000 patients outside of the US.

PRGN-2009 AdenoVerse Gene Therapy in HPV-associated cancers

PRGN-2009 is an investigational off-the-shelf AdenoVerse gene therapy designed to activate the immune system to recognize and target HPV-associated cancers.

· PRGN-2009 Phase 2 clinical trials under a 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.

PRGN-3006 UltraCAR-T in AML and MDS

PRGN-3006 is an investigational multigenic, autologous chimeric antigen receptor T cell (CAR-T) therapy engineered to simultaneously express a CAR specifically targeting CD33, membrane bound IL-15 (mbIL15), and a safety/kill switch. PRGN-3006 has been granted Orphan Drug Designation in patients with acute myeloid leukemia (AML) and Fast Track Designation in patients with relapsed/refractory (r/r) AML by the FDA.

· The Company has completed enrollment of the Phase 1b trial for PRGN-3006 in acute myeloid leukemia (AML), which received Fast Track designation from the FDA, and is preparing for an end of Phase 1b meeting with the FDA to discuss next steps.

Financial Highlights

· In December 2024, the Company raised $87.5 million, of which $79.0 million was from a private placement offering of convertible preferred stock, and an additional $8.5 million was from the sale of certain intellectual property and royalty rights related to a non-core asset.

· By year’s end 2024, cash, cash equivalents, and investments totaled $97.9 million.

Full Year 2024 Financial Results Compared to Prior Year Period

Total revenues decreased $2.3 million, or 37%, and cost of products and services decreased $1.8 million or 30% compared to the year ended December 31, 2023. These decreases were primarily related to reductions in product and service volumes at Exemplar.

Research and development expenses increased $4.5 million, or 9%, compared to the year ended December 31, 2023. This increase was primarily the result of $3.1 million of increased costs associated with the initiation of the PRGN-2012 confirmatory clinical trial, increased drug manufacturing material costs related to PRGN-2012 for potential commercial use, and professional fees incurred in conjunction with the Company’s completed BLA submission and commercial readiness planning as well as the design and implementation of our manufacturing facility. Additionally, employee-related expenses rose by $3.0 million primarily due to severance charges incurred as a result of the Precigen workforce reduction in 2024 and the suspension of ActoBio’s operations. These increases were partially offset by a $1.9 million reduction in depreciation and amortization expense as a result of the impairment of noncurrent assets related to the suspension of ActoBio’s operations during the second quarter of 2024 as well as a reduction in clinical study expenses associated with programs that were deprioritized during the third quarter of 2024.

SG&A expenses increased $0.9 million, or 2%, compared to the year ended December 31, 2023. As a result of the Company’s increased focus on PRGN-2012, commercial readiness costs increased in 2024 compared to the prior year. In addition, the second and third quarters of 2024 included higher severance costs associated with the suspension of ActoBio’s operations and the Precigen workforce reduction. These increases were partially offset by a decrease in stock compensation and insurance rates in 2024 compared to the same period in 2023.

The Company recorded a $5.8 million impairment charge in the fourth quarter of 2024 related to its Exemplar subsidiary as a result of the Company’s annual goodwill impairment test. Also, in conjunction with the suspension of ActoBio’s operations, the Company recorded $34.5 million of impairment charges related to goodwill ($1.6 million) and other noncurrent assets ($32.9 million) in the second quarter of 2024.

Total other income, net, increased $3.6 million, or 106% compared to the year ended December 31, 2023. This increase was primarily derived from an $8.5 million gain on the sale of intellectual property rights and royalty rights related to a non-core asset in December 2024 as well as a $0.5 million reduction in interest expense due to the final retirement of the Company Convertible Notes in the second quarter of 2023. This increase was partially offset by a reclassification of cumulative translation losses of $2.9 million, which resulted from the final closing of the ActoBio facilities in the third quarter of 2024, as well as a reduction of $1.8 million in interest income compared to the same period in 2023.

Net loss was $126.2 million, or $(0.47) per basic and diluted share, compared to net loss of $95.9 million, or $(0.39) per basic and diluted share, in year ended December 31, 2023.

On March 19, 2025 Sonnet BioTherapeutics Holdings, Inc. (the "Company" or "Sonnet") (NASDAQ: SONN), a clinical-stage company developing targeted immunotherapeutic drugs, reported that the United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance to the Company for a second patent in the IL-18 variant protein field which discloses the amino acid sequence of its variant human IL-18BPR protein (Press release, Sonnet BioTherapeutics, MAR 19, 2025, View Source [SID1234651261]). The allowed patent claims cover variant human IL-18 (hIL-18) proteins, including but not limited to hIL-18 proteins having amino acid substitutions at the following positions: Y1W, Y1K, M51Y, M51S, M60W, S105E, and D110Y, relative to human wildtype IL-18. Additionally, the Company announced the release of a Virtual Investor "What This Means" segment to discuss the allowed patent, which is now available here.

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"I believe that Sonnet has become of one of the few companies that hold proprietary rights to IL-18BPR which could be a highly valuable cytokine for cancer patients. This patent covers the composition of matter of the amino acid sequence of our human IL-18BPR variant protein which bolsters our intellectual property position and provides further validation to our approach that when IL-18BPR is synergistically combined with IL-12, we believe we will have the potential to develop an important therapeutic asset for oncology and cell-based therapy. Additionally, we feel that this patent enables us to explore opportunities for IL-18BPR to be licensed independent of our FHAB platform. We continue to believe that novel bifunctional molecules such as SON-1411, when combined with our proprietary FHAB platform, have the potential to demonstrate improved tumor targeting, extended half-life and an enhanced therapeutic window," said Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Officer.

Sonnet previously reported the generation of two novel drug candidates, SON-1411 (IL18BPR-FHAB-IL12) and SON-1400 (IL18BPR-FHAB), each containing a variant version of recombinant human interleukin-18 (IL-18BPR). SON-1411 is a proprietary bifunctional fusion protein consisting of IL-18BPR combined with single-chain wild-type IL-12, linked to Sonnet’s Fully Human Albumin Binding (FHAB) platform while SON-1400 is a monofunctional fusion protein comprising the same IL-18BPR domain linked to the FHAB. FHAB extends the half-life and biological activity of linked molecules by binding native albumin in the serum and targets the tumor microenvironment (TME) through high affinity binding to glycoprotein 60 (gp60) and the Secreted Protein Acidic and Rich in Cysteine (SPARC).

"SON-1411 (IL18BPR-FHAB-IL12) is a bifunctional combination of IL-12 and the FHAB domain with a human variant of human interleukin-18 ("IL-18BPR"), which was modified to resist an inhibitory interaction with IL-18 binding protein (IL-18BP). IL-18 is involved in activating both innate and adaptive immune responses; however, IL-18 clinical therapies have been hampered by a lack of efficacy due to the inhibitory activity of the IL-18BP," commented John Cini, Ph.D., Sonnet Chief Scientific Officer.

About SON-1411

SON-1411 is a candidate immunotherapeutic recombinant drug that is closely related to and will replace SON-1410, which links an unmodified single-chain human IL18 and an unmodified IL-12 with the albumin-binding domain of the single-chain antibody fragment A10m3. The only difference between SON-1410 and SON-1411 is that in the latter, the IL-18 domain has been modified via mutagenesis to retain wildtype binding to the IL-18 receptor (IL-18 Rc) while inhibiting or abolishing binding to the IL-18 binding protein (IL-18 BP). The A10m3 scFv was selected to bind both at normal pH, as well as at the acidic pH that is typically found in the TME. The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of IL-18 and IL-12, as well as a variety of potent immunomodulators that can be added using the platform. Interleukin-12 can orchestrate a robust immune response to many cancers and pathogens. Given the types of proteins induced in the TME, such as SPARC and gp60, several types of cancer such as non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant for this approach. SON-1411 is designed to deliver IL-18BPR and IL-12 to local tumor tissue, turning ‘cold’ tumors ‘hot’ by stimulating IFNγ, which activates innate and adaptive immune cell responses and increases the production of Programed Death Ligand 1 (PD-L1) on tumor cells.

On March 19, 2025 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it launched "LUNSUMIO for intravenous infusion 1 mg" and "LUNSUMIO for intravenous infusion 30 mg" (generic name: mosunetuzumab (genetical recombination)) (hereafter, LUNSUMIO), antineoplastic agent / anti-CD20/CD3 humanized bispecific antibody for the treatment of patients with relapsed or refractory follicular lymphoma who have received two or more prior standard therapies (Press release, Chugai, MAR 19, 2025, View Source [SID1234651225]). LUNSUMIO had been approved by the Ministry of Health, Labour and Welfare (MHLW) on December 27, 2024 and was listed on the national health insurance (NHI) reimbursement price list today.

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"Relapsed or refractory follicular lymphoma is a difficult-to-cure disease that repeatedly relapses, and therefore there was a need for new treatment options. LUNSUMIO is expected to provide durable remission with monotherapy, and with a predetermined treatment duration based on each patient’s response to therapy, which can help reduce the burden of treatment on patients. We will strive to promote proper use in order to deliver new value to patients, their families, and healthcare professionals," said Chugai’s President and CEO, Dr. Osamu Okuda.

This approval is based on the results of a Japanese Phase I study with an expansion cohort (FLMOON-1 study) conducted in patients with relapsed or refractory follicular lymphoma who had received two or more prior standard therapies, as well as an overseas Phase I/II clinical trial conducted by Roche in the same patient population. In both studies, the efficacy and safety of this drug were evaluated as a monotherapy. Furthermore, four-year follow-up data from the overseas Phase I/II clinical trial was presented at the 66th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper).

Approval Information

Product name: "LUNSUMIO for intravenous infusion 1 mg" and "LUNSUMIO for intravenous infusion 30 mg"

Generic name: mosunetuzumab (genetical recombination)

Indications: relapsed or refractory follicular lymphoma

Precautions concerning indications:

Treatment with this drug should be targeted at patients who have failed to respond to or have relapsed after two or more standard therapies, including an anti-CD20 monoclonal antibody product.
This drug should be administered to patients diagnosed with Grade 1-3A by a pathologist with sufficient experience.
Dosage and administration:
For adults, the usual dosage of mosunetuzumab (genetically modified) is administered as an intravenous infusion in 21-day cycles as follows:
Cycle 1: 1 mg on Day 1, 2 mg on Day 8, and 60 mg on Day 15
Cycle 2: 60 mg on Day 1
Cycles 3-8: 30 mg on Day 1 of each cycle
After 8 cycles, treatment should be discontinued for patients who achieve a complete response. For patients with stable disease or partial response, treatment may be continued for up to a total of 17 cycles.

Date of approval: December 27, 2024

Date of NHI reimbursement price listing: March 19, 2025

Date of launch: March 19, 2025

Drug price:
LUNSUMIO for intravenous infusion 1 mg　　JPY 83,717 / bottle
LUNSUMIO for intravenous infusion 30 mg　 JPY 2,393,055 / bottle

Reference

Chugai Obtains Regulatory Approval for "LUNSUMIO for Intravenous Infusion" for Relapsed or Refractory Follicular Lymphoma in Japan (Press release December 27, 2024)
View Source

About LUNSUMIO

LUNSUMIO is a CD20/CD3 T cell-engaging bispecific antibody designed to target CD20 on B cells and CD3 on T cells. LUNSUMIO is expected to activate the immune system through cytotoxic T cells and have antitumor effects on CD20 expressing tumor cells. LUNSUMIO has been approved in 61 countries worldwide. LUNSUMIO is currently being developed for the treatment of follicular lymphoma (second-line treatment and previously untreated) and relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma.

About follicular lymphoma

Follicular lymphoma is a type of lymphoma that occurs when B lymphocytes, a type of white blood cell, become cancerous. At diagnosis, 70-85% of patients reach an advanced stage1. Generally, the progression is slow, and chemotherapy is initially effective, but recurrences occur repeatedly in many cases. Repeated recurrences can make it difficult for existing treatments to be effective, and new highly effective treatments are needed. In Japan, approximately 9,000 people reportedly become afflicted with follicular lymphoma each year.

On March 19, 2025 Tvardi Therapeutics, Inc. ("Tvardi"), a clinical-stage biopharmaceutical company developing novel STAT3 inhibitors for fibrosis-driven diseases, reported that results from the first-in-human Phase 1 study of TTI-101 in patients with advanced solid tumors have been published in the journal Clinical Cancer Research (Press release, Tvardi Therapeutics, MAR 19, 2025, View Source [SID1234651262]).

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Imran Alibhai, Ph.D., Chief Executive Officer of Tvardi Therapeutics, stated, "The positive results of this Phase 1 study speak to the potential broad clinical utility of our lead candidate, TTI-101, across a range of fibrosis-driven diseases in which STAT3-mediated proliferation is implicated. Perhaps most notable, in addition to its biological activity in advanced treatment-refractory hepatocellular carcinoma, was a pharmacodynamic reduction of TTI-101’s target, activated STAT3, within paired tumor biopsies. We believe these findings provide very strong rationale for our ongoing Phase 2 studies in IPF and liver cancer."

The publication, titled, "Phase 1 Trial of TTI-101, a First-in-Class Oral Inhibitor of STAT3, in Patients with Advanced Solid Tumors," describes a Phase 1 study in which patients, who received a median of three prior systemic therapies, were treated with TTI-101 monotherapy orally twice daily (NCT03195699). By targeting both intrinsic tumorigenesis and extrinsic immune suppression, TTI-101 showed promising antitumor activity across tumor types, particularly in patients with hepatocellular carcinoma who were refractory to immune checkpoint inhibitors and anti-angiogenic agents.

TTI-101 showed dose-linear pharmacokinetics and, at the recommended Phase 2 dose, the trough exposure levels were above the IC90 for STAT3-induced growth. No dose-limiting toxicities or treatment-related adverse events greater than grade 3 were observed. Pharmacodynamic analysis demonstrated TTI-101 decreased levels of phosphotyrosine (pY) STAT3 within paired tumor biopsies.