On November 14, 2024 Nerviano Medical Sciences S.r.l. (NMS) – a part of NMS Group S.p.A. (NMS Group) and Nerviano Medical Sciences, Inc., a wholly owned subsidiary of NMS Srl – a global leader in oncological innovation with a leading position in PARP1 inhibitor clinical development in brain cancer, reported the acquisition of atamparib, the first selective PARP7 inhibitor (Press release, Nerviano Medical Sciences, NOV 14, 2024, View Source [SID1234648503]). This transaction highlights NMS’s commitment to solidify its leadership in PARP biology and expanding its pipeline with transformative cancer therapies designed to meet significant unmet medical needs.

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!

Strategic Enhancement of Oncology Portfolio: Atamparib is currently in Phase II with the potential to be first-in-class. This PARP7 inhibitor enriches NMS’s diverse range of small molecules in the portfolio developed for various types of cancers. PARP7, a crucial target in oncology, is upregulated in response to cellular stress, promoting cancer cell survival. By targeting PARP7 in tumor cells, atamparib has been shown to inhibit cellular proliferation. It is an orally bioavailable small molecule with high potency on pre-clinical models, and a favorable safety and tolerability profile in PhI/II studies.

Leveraging Expertise in PARP Biology: NMS brings extensive knowledge in PARP biology, demonstrated through the development of NMS-293, an oral potent and selective PARP1 inhibitor with non-trapping effects and brain penetrant properties. NMS-293 has shown promising clinical activity in a Ph I/II study in combination with temozolomide in recurrent glioblastoma and astrocytoma patients. Building on this expertise and foundational research conducted by Ribon Therapeutics, NMS will advance the atamparib program into an innovative and effective therapy. This initiative reinforces NMS leadership in the development of PARP inhibitors.

Dr. Hugues Dolgos, CEO of Nerviano Medical Sciences, commented: "We are excited about the addition of atamparib to our pipeline. NMS has been working on PARP7 for a long time, therefore, we believe that we are in a unique position to leverage our knowledge during the clinical development of atamparib. The very recent scientific evidence of the PARP7 biology is directing us to a different setting in which we believe we can demonstrate proof of concept in the clinical trials we plan to initiate in 2025".

On November 14, 2024 Defence Therapeutics Inc. ("Defence" or the "Company"), (CSE:DTC, OTCQB: DTCFF, FSE: DTC) a Canadian biopharmaceutical company developing radiopharmaceuticals and ADC products using its proprietary platform and drug delivery technologies in addition to novel immune-oncology vaccines, reported that it offers new unsecured convertible debentures (the "New Debentures") for aggregate gross proceeds of up to CAD$1,570,000 (the "Offering") in consideration for the settlement of the principal amounts owing to holders of the Previous Debentures (as defined below) (the "Outstanding Debt") (Press release, Defence Therapeutics, NOV 14, 2024, View Source;utm_medium=rss&utm_campaign=defence-therapeutics-announces-securities-for-debenture-financing [SID1234648440]).

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 New Debentures will be issued on a non-brokered private placement basis, bear interest at the rate of 8.0% per annum, be subject to a Conversion Event (as defined below), and mature on November 16, 2025 (the "Maturity Date"). Each New Debenture is unsecured and rank pari passu in right of payment of principal and interest with all the existing and future unsecured indebtedness of the Company. The principal amount of each New Debenture is convertible at the option of the holder into common shares in the capital of the Company (the "Common Shares") at a price of $0.60 per Common Share at any time up to and including the Maturity Date (the "Conversion Event"). Assuming each New Debentures holder exercises their respective Conversion Event, the Company would issue an aggregate total of 2,616,666 Common Shares to the holders thereof.

The Outstanding Debt was incurred in connection with the Previous Debentures that were underlying previously issued units of the Company (the "Units") at a price of $1,000 per Unit on November 16, 2022. Each Unit consisted of: (i) one $1,000 principal amount 8.0% convertible debenture (the "Previous Debenture"), and (ii) 636 common share purchase warrants.

Upon closing of the Offering, their will be no Previous Debentures outstanding; and concurrent with the closing of the Offering, the total accrued interest owing on the Previous Debentures in the amount of approximately $251,200 will be settled via the conversion of such outstanding amount into Common Shares at a price per share equal to the closing market price of the Common Shares as of the trading day prior to such issuance, and in accordance with the terms and conditions of the Previous Debentures.

All securities issued in connection with the Offering are subject to a statutory hold period of four months plus a day in accordance with applicable securities legislation. The closing of the Offering and issuance of the New Debentures and the Common Shares to settle outstanding interest owing from the Previous Debentures are subject to receipt of all necessary regulatory and corporate approvals, including but not limited to approval from the Canadian Securities Exchange.

On November 14, 2024 TriSalus Life Sciences Inc., (Nasdaq: TLSI), an oncology company integrating novel delivery technology with immunotherapy to transform treatment for patients with liver and pancreatic tumors, reported its financial results for the third quarter ended September 30, 2024, and provided a business update (Press release, TriSalus Life Sciences, NOV 14, 2024, View Source [SID1234648426]).

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!

"We enter the final quarter of 2024 with great momentum, both commercially and clinically, and we are positioned well for an even greater 2025," stated Mary Szela, President and Chief Executive Officer of TriSalus Life Sciences. "Commercially, we enjoyed a strong third quarter highlighted by 42% revenue growth. We recently launched the TriNav LV system to address patients with larger vessels, an opportunity we believe will meaningfully expand our addressable market and provide full access to the $375 million liver embolization market."

"With the successful completion of our Phase 1 dose escalation study enrollment in UM-LM, we are actively pursuing a strategic partnership for nelitolimod," continued Ms. Szela. "This follows the successful presentation of positive Phase 1 results from our PERIO-01 dose escalation study in UM-LM at SITC (Free SITC Whitepaper). Additionally, by mid-2025, we anticipate data from our Phase 1 study in locally advanced pancreatic cancer, which will guide our next steps."

"Our clinical development efforts for the TriNav system have expanded with the launch of the DELIVER program, starting with the PROTECT registry trial for patients with multinodular goiter. There is significant potential to broaden our addressable market by $400 million, and we are committed to providing further updates on PROTECT and additional programs within the DELIVER initiative."

"Finally, we are initiating 2025 guidance that calls for greater than 50% revenue growth, a greater than 20% reduction in operating expenses, positive full-year EBITDA, and positive cash flow in the second half of the year," concluded Ms. Szela.

Third Quarter Business Update

TriNav System Large Vessel Launch

TriSalus recently expanded its portfolio of Pressure-Enabled Drug Delivery (PEDD) devices with the launch of the TriNav LV Infusion System and TriGuide Guiding Catheter to optimize therapeutic delivery for patients with larger vessels. The TriNav LV system is suitable for patients with vessels sized between 3.5 and 5.0 mm and is expected to allow the Company to meaningfully expand its addressable liver embolization market. The TriGuide Guiding Catheter has a larger inner diameter, lubricious inner lining, and reverse curve design to support femoral access for the TriNav LV system, which the Company believes will enhance procedural efficiency. These new products are eligible for the same HCPCS reimbursement codes as existing TriNav products, enabling seamless integration into current billing structures.

DELIVER and PROTECT Updates

During the quarter, TriSalus advanced the DELIVER clinical program, a series of clinical trials designed to demonstrate enhanced safety and efficacy across a broad spectrum of complex, difficult-to-treat patients through investigator-initiated studies, further underscoring the impact of PEDD technology. A key focus of the DELIVER program is to investigate the potential of combining use of the TriNav system with these therapies to enhance effectiveness and address resistance mechanisms in challenging cancers.

The first of these is a registry study called PROTECT (Pressure Enabled Retrograde Occlusive Therapy with Embolization for Control of Thyroid Disease), which has been initiated, and TriSalus intends to enroll 100 patients across five leading academic sites. It is estimated that approximately 5% of adults have multinodular goiters, and the prevalence in adults over 50 is estimated to be up to 50%. The Company estimates that this could expand the addressable market by approximately 50,000 procedures, representing an incremental $400 million market opportunity and putting the Company’s total addressable market at more than $1 billion in the U.S. This new procedure utilizing the TriNav system is also eligible for the same Healthcare Common Procedure Coding System (HCPCS) reimbursement code allowing for seamless integration into current billing approaches.

The Company anticipates opening additional DELIVER studies in the first half of 2025 and will provide more details as those studies commence.

PERIO Trial Update

TriSalus presented Phase 1 results from the PERIO-01 clinical trial at the recent SITC (Free SITC Whitepaper) meeting. This dose escalation trial investigated the use of the PEDD method of nelitolimod in patients with UM-LM. The results suggested that PEDD-administered nelitolimod, combined with immune checkpoint inhibitors, provides promising clinical benefits and durable survival in heavily pretreated patients with UM-LM and a favorable safety profile. The Company is actively exploring strategic partnerships to advance this indication further.

The Company also completed enrollment of 13 patients in its PERIO-03 Phase 1 dose escalation study of nelitolimod in locally advanced pancreatic cancer. Evidence gathered thus far supports a strong safety profile and further exploration of nelitolimod combined with the TriNav pancreatic infusion technology. The Company will outline the next steps once the final data are available in mid-2025.

Financial Results for Q3 2024

Revenue, all from the sale of the TriNav system, was $7.3 million and $21.2 million, respectively, for the three and nine months ended September 30, 2024. These were up 42% and 66%, respectively, compared to the same periods in 2023. Revenue growth was driven primarily by increased selling resources and increased market share.

Gross margins were 86% and 86% for the three and nine months ended September 30, 2024, respectively, compared to 89% and 84%, respectively, for the same periods in 2023. The year-to-date improvement is due to increased factory volumes and improved operational efficiency.

Operating losses were $8.7 million and $28.6 million, respectively, for the three and nine months ended September 30, 2024, respectively, compared to losses of $18.6 million and $40.2 million, respectively, for the same periods in 2023. These amounts include non-cash stock compensation and depreciation expenses of $1.6 million and $4.3 million for the three- and nine-month periods in 2024 and $0.4 million and $0.9 million for the same periods in 2023. Current year reductions in operating losses are due to increased sales, reduced general and administrative expenses due to non-recurrence of prior year costs related to becoming a public company, and reduced research and development spending associated with the ramp-down of clinical trial spending.

Net losses available to common stockholders were $2.4 million and $19.9 million, respectively, for the three and nine months ended September 30, 2024, compared to losses of $1.4 million and $23.7 million, respectively, for the same periods in 2023. Net losses in 2024 include non-cash related gains on change in fair value of various derivatives of $7.3 million and $10.5 million, respectively, for the three and nine months ended September 30, 2024, compared to gains of $17.1 million and $16.4 million, respectively, for the same periods in 2023. The basic and diluted loss per share for the three and nine months ended September 30, 2024, were $0.12 and $0.91, respectively, compared to $0.14 and $5.72 for the three and nine months ended September 30, 2023, respectively.

On September 30, 2024, cash and cash equivalents totaled $11.3 million. The Company expects existing liquidity sources and $25 million of available capacity on the OrbiMed debt facility to provide sufficient cash runway throughout 2025. In addition, the company expects to be EBITDA positive for 2025 and achieve positive cash flow by the second half of 2025, extending total cash runway beyond 2025.

2025 Guidance

The Company is providing guidance for 2025 for the first time, including:

Sales are expected to grow by more than 50% in 2025, driven by further market share increases in the TriNav system, the commercial launch of the TriNav LV system, and the TriNav target market expansion driven by the DELIVER program.
Operating expenses are expected to decline greater than 20% in 2025 due to reductions in R&D associated with completing the PERIO Phase 1 trials and reductions in G&A expenses due to the non-recurrence of certain costs related to becoming a public Company.
The Company expects to achieve positive full-year EBITDA and positive cash flow in the second half of the year.
Conference Call

TriSalus will host a webcast to discuss its third quarter 2024 financial results and business highlights on November 14, 2024, at 9:00 a.m. EST. The webcast can be accessed on the investor relations section of TriSalus’ website at View Source Following the conclusion of the event, a webcast replay will be available on the website. Interested parties participating by phone will need to register using this online form. After registering for the webcast, dial-in details will be provided in an auto-generated e-mail containing a link to the conference phone number and a personal pin.

On November 14, 2024 IDRx, Inc., a clinical-stage biopharmaceutical company dedicated to developing and commercializing precision therapeutics for the treatment of cancers with well-characterized biology and significant unmet medical need, reported updated clinical data from StrateGIST 1, the company’s ongoing Phase 1/1b trial of IDRX-42 in patients with advanced gastrointestinal stromal tumors (GIST) (Press release, IDRx, NOV 14, 2024, View Source [SID1234648425]). These data continue to demonstrate promising anti-tumor activity of IDRX-42 in patients with advanced GIST and will be highlighted today in an oral presentation at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting, being held November 13-16, in San Diego, CA.

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!

IDRX-42 is an investigational oral, small molecule, tyrosine kinase inhibitor (TKI) designed to selectively target the most prevalent KIT mutations that either drive the growth, proliferation, and survival of tumor cells (activating mutations in exons 9 and 11), or confer resistance to currently available therapies (resistance mutations in exons 13 and 17).

"In patients living with GIST, the therapeutic potential of KIT targeted TKIs has been limited by drug resistance caused by an inability to target the spectrum of the most prevalent KIT mutations, and poor tolerability," said Suzanne George, M.D., Chief, Division of Sarcoma at the Dana-Farber Cancer Institute. "These updated data from StrateGIST 1 are highly encouraging with respect to the clinical activity observed in later-line patients with a variety of KIT activating and resistance mutations. I am excited by the potential of IDRX-42, with its differentiated clinical profile demonstrated to date, to help meet this critical need for GIST patients."

"We are particularly excited about the emerging durability data from StrateGIST 1. These data, together with the continued strengthening of response rate and tolerability data, underscore the potential for IDRX-42 to improve outcomes for GIST patients and support our plans to move IDRX-42 into late-phase development," said Tim Clackson, Ph.D., Chief Executive Officer of IDRx. "With FDA alignment now in place, we plan to conduct StrateGIST 3, a randomized, Phase 3 registrational trial which will evaluate the efficacy and safety of IDRX-42 as compared to sunitinib in second-line GIST patients. We remain steadfast in our commitment to transform the lives of patients with GIST, including in early-line settings, where the standards of care have remained unchanged for almost 20 years and a significant unmet need remains."

Presentation Highlights

As of the data cut-off date of September 30, 2024, 89 patients have been treated with IDRX-42 in the Phase 1 portion of the ongoing StrateGIST 1 trial across dose cohorts ranging from 120 mg once daily (QD) to 1200 mg total daily dose (600 mg twice daily (BID)). All 89 patients had KIT-mutant GIST. 87 patients were evaluable for efficacy as of the data cut-off date. The two non-evaluable patients were recently enrolled and remain on treatment, awaiting their first post-baseline tumor assessment.
While a maximum tolerated dose was not reached, dose escalation in the Phase 1 portion of the trial has been completed, and the Phase 1b dose confirmation portion of the trial has been initiated utilizing a dose of 300 mg in tablet formulation, which has comparable steady-state plasma exposure to a dose of 400 mg in capsule formulation.
Patients were heavily pretreated overall, with a median of four prior lines of therapy.
17% (15/89) patients had received one prior line of therapy (IDRX-42 evaluated as second-line).
11% (10/89) patients had received two prior lines of therapy (IDRX-42 evaluated as third-line).
72% (64/89) patients had received three or more prior lines of therapy (IDRX-42 evaluated as ≥ fourth-line).
28% (25/89) received three or more prior lines of therapy that did not include ripretinib.
As of the data cut-off date, 63% (56/89) of patients remained on study treatment, and the median duration of treatment was 6.6 months.
The ORR by modified RECIST v1.1 in the total efficacy evaluable population was 29% (25/87) treated across all lines of therapy, including one complete response (CR) and 24 partial responses (PRs). Two of the PRs were awaiting confirmation at the time of the data cut.
At the 400 mg capsule/300 mg tablet QD recommended Phase 1b dose (RP1bD), the ORR was 26% (10/38) in the total efficacy evaluable population.
The ORR in second-line patients was 53% (8/15) including one CR and 7 PRs.
At the RP1bD or below, the ORR was 50% (7/14) across second-line patients.
In second-line patients (n=15), the 6-month PFS was 85%, and the median was not yet reached.
The median PFS in third- or later-line patients both at the RP1bD (n=25) and across all doses (n=72) was 9.2 months.
The median PFS in third-line patients overall (n=10) was 12.9 months.
The median PFS in fourth- or later-line patients who had not previously received ripretinib (n=25) was 9.2 months, and at the RP1bD (n=10) was 11 months.
IDRX-42 was generally well-tolerated and treatment-related adverse events (TRAEs) were mainly low grade at the RP1bD.
The most frequently reported TRAEs (≥20%) were gastrointestinal symptoms (diarrhea, nausea, decreased appetite, vomiting, dysgeusia) and fatigue.
An 8% dose reduction rate due to TRAEs was observed at RP1bD, with no TRAEs leading to dose discontinuation.
The Phase 1b portion of StrateGIST 1 commenced enrollment in May 2024 and includes a first-, second-, and two later-line cohorts. The second- and two later-line cohorts are nearly fully enrolled. IDRx has aligned with the FDA on fundamental elements of the trial design, dose, and statistical analysis for StrateGIST 3, a global, randomized, Phase 3 registrational trial which will evaluate IDRX-42 as a second-line therapy in patients diagnosed with metastatic and/or unresectable GIST with disease progression on, or intolerance to, imatinib, the current first-line standard of care for GIST patients.

Presentation Details
Title: The Novel KIT inhibitor IDRX-42 Shows Promising Activity in Second- and Later-Line Gastrointestinal Stromal Tumors (GIST): Results from a Phase 1 Trial (StrateGIST 1)
Presenter: Suzanne George, M.D.
Abstract Number: P 10
Presentation Type: Oral Abstract Session
Time: Thursday, November 14, 10:30 a.m. – 11:30 a.m. PST
Location: Harbor Ballroom, Manchester Grand Hyatt, San Diego, CA

About GIST
Gastrointestinal stromal tumor (GIST) is the most common subtype of soft tissue sarcoma occurring in the gastrointestinal tract. Between 4,000 to 6,000 people are diagnosed with GIST in the United States each year. Approximately 80% of all GIST cases are driven by mutations in the KIT gene. An estimated 90% of patients who receive imatinib, the current standard of care for GIST, will experience disease progression related to the emergence of KIT resistance mutations. In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type. Despite the widespread availability of tyrosine kinase inhibitors approved for GIST, first-line and second-line standards of care have remained unchanged for almost 20 years and significant unmet need remains.

About the StrateGIST 1 Study
StrateGIST 1 is an ongoing, open-label, first-in-human Phase 1/1b study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of IDRX-42 in patients with metastatic and/or surgically unresectable GIST after progression on imatinib and other approved drugs. The study is currently enrolling patients with documented pathogenic mutation in KIT or any platelet-derived growth factor receptor alpha (PDGFRA) mutation (other than PDGFRA exon 18) at sites in the U.S., United Kingdom, Belgium, the Netherlands, France, Germany, Italy, Spain, South Korea, and China. The Phase 1b portion commenced enrollment in May 2024 and includes four exploratory cohorts based on defined lines of prior tyrosine kinase inhibitor therapy, including first-, second-, third- and later-line therapies.

About IDRX-42
IDRX-42 is an investigational oral, small molecule KIT tyrosine kinase inhibitor in clinical development as a monotherapy for the treatment of gastrointestinal stromal tumors (GIST). IDRX-42 is designed to selectively target the most prevalent forms of KIT mutations that either drive the initial growth, proliferation, and survival of tumor cells, or confer resistance to currently available therapies. In pre-clinical studies, IDRX-42 demonstrated superior anti-tumor activity as compared to imatinib, the current first-line of therapy, in tumors associated with both exon 9 and 11 KIT mutations. IDRX-42 was also shown in pre-clinical studies to have strong inhibition activity against the most prevalent KIT resistance mutations in exons 13 and 17, suggesting that IDRX-42 could prevent or substantially delay the emergence of such mutations. In xenograft models expressing secondary resistance mutations in KIT exon 13 or 17, IDRX-42 treatment resulted in potent and dose-dependent antitumor activity superior to the second-line standard of care agent, sunitinib. IDRX-42 is currently being evaluated in StrateGIST 1, a first-in-human Phase 1/1b trial. IDRX-42 has been granted Fast Track and Orphan Drug designations by the U.S. Food and Drug Administration for the treatment of GIST after disease progression on imatinib.

On November 14, 2024 GordonMD Global Investments LP reported that its portfolio company, Flare Therapeutics Inc., has entered into a strategic discovery collaboration with Roche (SIX: RO, ROG; OTCQX: RHHBY). Flare will lead discovery and preclinical activities targeting multiple transcription factor targets in oncology, while Roche will pursue the further preclinical and clinical development and commercialization of potential products from the collaboration, leveraging its industry-leading capabilities in oncology (Press release, Flare Therapeutics, NOV 14, 2024, View Source [SID1234648424]).

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!

Combining Flare’s advanced proteomic and mass spectrometry platform — powered by its proprietary library of electrophilic compounds — to discover small molecule drugs targeting transcription factors previously deemed yet to be affected by drugs in oncology with Roche’s experience in developing and manufacturing medicines, this collaboration seeks to advance potentially transformative therapies for patients living with cancer.

Flare will receive a US$70 million upfront cash payment and is eligible to receive discovery, development, and commercialization milestone payments potentially exceeding US$1.8 billion and royalties. Additionally, Flare retains a right to co-fund development for one target under the collaboration in exchange for increased royalties in the United States for this target. Flare will retain ownership of its existing pipeline, including its lead clinical-stage program, FX-909, in advanced urothelial cancer, its prostate cancer program entering IND-enabling studies, and other programs in discovery and early development in oncology and other therapeutic areas.

"This collaboration reinforces Flare’s capacity to advance its breakthrough science," said Dr. Craig Gordon, Chief Executive Officer of GordonMD.

"We look forward to our partnership with Roche because we share a commitment to tackling the most challenging disease areas with novel approaches and overcoming the difficulties of drugging transcription factors," said Rob Sims, Ph.D., Chief Scientific Officer and Co-founder of Flare Therapeutics.