On October 23, 2024 Rakovina Therapeutics Inc. (TSX-V: RKV), a biopharmaceutical company committed to advancing new cancer therapies based on novel DNA-damage response (DDR) technologies, reported that it has received initial results from the proprietary Deep Docking AI platform (Press release, Rakovina Therapeutics, OCT 23, 2024, View Source;utm_medium=rss&utm_campaign=rakovina-therapeutics-announces-initial-drug-candidates-from-deep-docking-ai-molecule-discovery-platform [SID1234647340]).

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Rakovina employed the Deep Docking algorithm to evaluate billions of molecular structures to develop a short-list of drug candidates that have been optimized to a specific target-product profile. A screening effort of this magnitude would not be possible with traditional medicinal chemistry approaches.

"With the Deep Docking AI platform, these initial results were achieved in less than five months versus traditional methods of discovery which would take thousands of years," said Rakovina Therapeutics Executive Chairman Jeffrey Bacha. "AI dramatically increases speed and the likelihood of success of our drug discovery platform," he added.

"We are pleased to receive this short-list of recommended drug candidates from our initial AI screening effort," said Bacha. "Our excitement is similar to receiving a core sample from a promising mining project, but instead of rare metals, this sample contains a curated list of potential novel best-in-class drug candidates that could provide significant improvements in the treatment of cancer for patients worldwide."

Selected drug candidates will be synthesized for validation in Rakovina Therapeutics’ laboratories at the University of British Columbia during the coming months with the goal of advancing a best-in-class DDR drug candidate to human clinical trials in collaboration with pharmaceutical company partners.

In March 2024, the Company announced that it was entering into a collaboration agreement with Dr. Artem Cherkasov, granting Rakovina Therapeutics exclusive access to the Deep Docking AI Platform for DNA-damage response targets. Dr. Cherkasov is a professor at the University of British Columbia (UBC) and a senior scientist at the Vancouver Prostate Centre. These results are the initial output of the ongoing collaboration.

The goal of the collaboration is to leverage AI algorithms to analyze billions of potential drug candidates, with the goal of accelerating discoveries, reducing costs, and improving the success rate in identifying best-in-class drug candidates in the DNA-damage response field. The agreement provides Rakovina with ownership rights to all novel drug candidates generated through the collaboration.

Rakovina Therapeutics will present the initial results of this research in a poster presentation at the Society for Neuro-Oncology Annual Meeting, which is being held November 21 through 24, 2024, at the George R. Brown Convention Center in Houston, Texas.

Additionally, in Sept. 2024, the Company announced an agreement with Variational AI of Vancouver to leverage the capabilities of the Enki AI platform which has been trained to identify novel inhibitors of specific kinase targets in the DDR field. Rakovina Therapeutics expects initial results from this research in the next several months.

On October 23, 2024 Nimbus Therapeutics, LLC ("Nimbus Therapeutics" or "Nimbus"), a biotechnology company that designs and develops breakthrough medicines for patients through its powerful computational drug discovery engine, reported that it is presenting preclinical data on its new development candidate, NTX-452, a novel Werner syndrome helicase (WRN) inhibitor, at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics, taking place October 23-25, 2024 in Barcelona, Spain (Press release, Nimbus Therapeutics, OCT 23, 2024, View Source [SID1234647339]).

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WRN is a helicase required for DNA replication and DNA repair and is a validated target for tumors with microsatellite instability (MSI). MSI is a phenotypic consequence of defective mismatch repair (dMMR) and occurs in various tumor types, including colorectal, gastric and endometrial cancers. Inhibition of WRN activity has the potential to induce synthetic lethality in MSI-high (MSI-H) tumors. Using a structure-based drug design approach, Nimbus developed highly potent and selective covalent and non-covalent inhibitors of WRN, and has selected a novel non-covalent inhibitor, NTX-452, as the clinical candidate.

In a poster (abstract #356) titled "Preclinical Characterization of NTX-452, a Potent, Selective and Highly Efficacious WRN Inhibitor for the Treatment of MSI-H Tumors," Nimbus is presenting new data from preclinical assays and several tumor models that support the potential of the company’s non-covalent WRN inhibitor as a treatment for MSI-H tumors.

Key findings from the preclinical studies include:

NTX-452 demonstrated potent and selective inhibition of WRN activity with favorable drug-like properties.
The compound showed synthetic lethality in MSI-H tumor cells, triggering a DNA damage response that suppressed cell viability and promoted cell death.
Treatment with NTX-452 at low doses in vivo exhibited a robust pharmacodynamic response, resulting in tumor regression across multiple MSI-H cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) tumor models, including established models for colorectal, gastric and endometrial cancers.
Significant tumor regression and complete responses were observed at low oral doses in MSI-H models refractory to immunotherapy and chemotherapy.
"These compelling preclinical results for NTX-452 further highlight the significant potential of our WRN inhibitor as a promising therapeutic approach for patients with MSI-H tumors, many of whom fail to respond to or eventually relapse with current standard of care therapies including immune checkpoint inhibitors," said Peter Tummino, Ph.D., Chief Scientific Officer of Nimbus. "Our novel non-covalent approach to WRN inhibition, coupled with the robust efficacy demonstrated across diverse tumor types and treatment settings, positions our program for potential best-in-class status. We are particularly encouraged by the low doses required to achieve robust anti-tumor activity in preclinical models, which may translate to an improved benefit-risk profile in the clinic."

The preclinical profile of NTX-452 suggests several potential advantages in the treatment of MSI-H tumors, including:

The non-covalent mechanism may offer more durable on-target activity, and a greater safety window compared to covalent inhibitors.
High potency and favorable pharmacokinetic properties indicate the potential for target levels of efficacy at lower doses.
Broad efficacy across treatment-naïve, chemotherapy-pretreated, and immunotherapy-pretreated models suggests potential utility in both early-stage and advanced disease settings.
Activity in multiple MSI-H tumor types, including those with diverse genetic alterations, indicates potential broad applicability across dMMR/MSI-H cancers.
Nimbus is advancing NTX-452 with plans to enter the clinic in the first half of 2025.

On October 23, 2024 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported the upcoming presentation of new preclinical data supporting the combination of its next-generation farnesyl transferase inhibitor (FTI) KO-2806 with targeted therapies, including KRASG12C inhibitors and pan-RAS inhibitors, at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain (Press release, Kura Oncology, OCT 23, 2024, View Source [SID1234647338]).

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"We look forward to presenting an update to our growing body of preclinical and clinical data that demonstrate the potential of KO-2806 as a companion therapeutic to augment the antitumor activities of KRASG12C and pan-RAS inhibitors," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "These findings support the promising therapeutic strategy of blunting the effects of innate and adaptive resistance to targeted agents to treat cancers driven by KRAS mutations, including KRASG12C non-small cell lung cancer (NSCLC) and KRAS-mutant colorectal cancers. If successful, we believe KO-2806 could drive enhanced antitumor activity and become a combination partner to multiple targeted therapies in large solid tumor indications."

Details for the session titles and information for the two abstracts are listed below. Copies of the presentations will be available in the Posters and Presentations section on Kura’s website following presentation at the conference.

KO-2806, a next-generation farnesyl transferase inhibitor, re-sensitizes KRAS G12C NSCLC tumors to KRAS G12C mutant-specific inhibitors through mTOR signaling inhibition
Session Date and Time: Friday, October 25, 2024; 9:00 AM – 3:00 PM ET
Session and Location: Drug Resistance and Modifiers, Exhibition Hall
Poster Number: PB376

The next-generation farnesyl transferase inhibitor KO-2806 sensitizes colorectal cancers to pan-RAS inhibition
Session Date and Time: Friday, October 25, 2024; 9:00 AM – 3:00 PM ET
Session and Location: Drug Resistance and Modifiers, Exhibition Hall
Poster Number: PB378

About KO-2806

KO-2806 is a next-generation inhibitor of farnesyl transferase designed to improve upon the potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates. At the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), Kura presented preclinical data supporting the rationale for combining KO-2806 with distinct classes of targeted therapies, including tyrosine kinase inhibitors, KRASG12C inhibitors and KRASG12D inhibitors. Kura is evaluating KO-2806 in a Phase 1 dose-escalation trial (FIT-001) as a monotherapy, in combination with cabozantinib in clear cell renal cell carcinoma and in combination with adagrasib in KRASG12C NSCLC. Additional information about clinical trials for KO-2806 can be found at View Source

On October 23, 2024 Ipsen (Euronext: IPN; ADR: IPSEY), a global specialty-care biopharmaceutical company, reported its performance for the year to date and the third quarter of 2024 (Press release, Ipsen, OCT 23, 2024, View Source [SID1234647337]).

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YTD 2024 YTD 2023 % change Q3
2024 Q3
2023 % change
€m €m Actual CER1 €m €m Actual CER1
Oncology 1 829,8 1 744,1 4,9% 5,8% 604,0 574,5 5,1% 5,6%
Neuroscience 536,4 489,0 9,7% 11,8% 181,9 164,8 10,4% 10,1%
Rare Disease 129,7 76,0 70,7% 71,3% 50,8 33,2 53,1% 54,4%
Total Sales 2 495,9 2 309,1 8,1% 9,2% 836,6 772,4 8,3% 8,6%
Highlights

Total-sales growth in the year to date of 9.2% at CER1, or 8.1% as reported, with notable performances from Dysport (abobotulinumtoxinA), Cabometyx (cabozantinib) and Bylvay (odevixibat), with robust Somatuline (lanreotide) sales, as well as the increasing contribution from the launches of Iqirvo (elafibranor) in 2L PBC2 and Onivyde (irinotecan) in 1L mPDAC3
Regulatory approvals in the E.U. of Iqirvo and Kayfanda (odevixibat)
Increased 2024 financial guidance: total-sales growth greater than 8.0% at CER1 (prior guidance: greater than 7.0% at CER1); core operating margin greater than 31.0% of total sales (prior guidance: greater than 30.0%)
"Since the launch of our strategy in 2020, we have enjoyed uninterrupted growth. This quarter was no exception and was accompanied by further progress in the pipeline", commented David Loew, Chief Executive Officer. "We have also continued to launch across several indications and lines of therapy, including the recent rollouts of Iqirvo and Onivyde, which are progressing well. Supported by the performance so far this year, we are further increasing our 2024 sales and margin guidance."

"We have built a track record of delivery, grounded in a strong foundation of external innovation, commercial excellence and our ongoing mission to offer more choices for patients."

Full-year 2024 guidance

Based on the strong performance in the third quarter, Ipsen has further increased its financial guidance for 2024:

Total-sales growth greater than 8.0%, at constant currency (prior guidance of greater than 7.0%). Based on the average level of exchange rates in September 2024, an adverse impact on total sales of around 1.5% from currencies is expected
Core operating margin greater than 31.0% of total sales (prior guidance of greater than 30.0%)
Pipeline update

In September 2024, the European Commission conditionally approved Iqirvo 80mg tablets for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as a monotherapy in patients unable to tolerate UDCA. Iqirvo was approved in the same setting by the U.S. FDA in June 2024.

In September 2024, the European Commission also approved Kayfanda as a treatment for pruritus in children from as young as six months of age who have Alagille syndrome (ALGS). Odevixibat, under the brand name Bylvay, is already marketed in the E.U. for the treatment of progressive familial intrahepatic cholestasis (PFIC), and in the U.S. and E.U. for PFIC, and in the U.S. for ALGS.

In the same month, final results from the CABINET Phase III trial were presented at the 2024 European Society for Medical Oncology Congress and were published in the New England Journal of Medicine, reinforcing the efficacy benefits of Cabometyx in advanced neuroendocrine tumors. It was announced at that time that Ipsen had submitted an extension of indication Marketing Authorization to the European Medicines Agency.

Business development

In August 2024, Ipsen entered into an agreement to sell its rare pediatric disease Priority Review Voucher. As part of the agreement, Ipsen received a cash payment of $158m in the third quarter.

In October 2024, Eton Pharmaceuticals entered into an agreement with Ipsen to acquire Increlex (mecasermin injection). The transaction is expected to close before the end of 2024.

Arbitration proceedings with Galderma

As of 30 September 2024, two arbitration proceedings initiated by Galderma against Ipsen at the International Chamber of Commerce (ICC) were ongoing. The first dispute, initiated by Galderma in 2021, pertains to the territorial scope of the commercial partnership related to Azzalure (abobotulinumtoxinA) and Dysport under an agreement signed in 2007 in the E.U., in certain Eastern European countries, and in Central Asia. The Tribunal of the ICC Internal Court of Arbitration issued a final award, in October 2024, dismissing most, if not all, of Galderma’s claims in this first arbitration and ordered that Galderma bear the majority of the legal fees and arbitration costs incurred by Ipsen.
A second dispute was initiated by Galderma in November 2023, related to the validity of Ipsen’s 2023 termination of a joint R&D collaboration agreement entered into in 2014 under the parties’ respective early-stage neurotoxin programs, including the development of IPN10200. At this stage, Ipsen cannot reasonably predict any potential financial impact from this final remaining arbitration process, for which it intends to fully defend and vindicate its rights.

Conference call

A conference call and webcast for investors and analysts will begin today at 2pm CET. Participants can access the call and its details by registering here; webcast details can be found here.

On October 23, 2024 Interius BioTherapeutics, a clinical-stage company engineering targeted, programmable vectors for the precision delivery of genetic medicines, reported that the first study participant has been dosed in INVISE, its first-in-human Phase 1 clinical trial of INT2104, a first-in-class gene therapy that delivers a CAR transgene to generate effector CAR-T and CAR-NK cells in vivo for the targeting of CD20-positive B cells for the treatment of B-cell malignancies (Press release, Interius BioTherapeutics, OCT 23, 2024, View Source [SID1234647336]).

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"Interius was founded with a sense of urgency to provide patients with a new therapeutic option that does not require preconditioning or long manufacturing and wait times. Interius’s breakthrough technology allows precise targeting of gene therapies to specific cells via intravenous administration," said Interius President and CEO, Phil Johnson, M.D. "This milestone marks the first time that a durable in vivo CAR therapy has been used in the clinic. INT2104 has the potential to overcome ex vivo CAR therapy challenges with a single-dose, off-the-shelf, widely accessible therapy for the treatment of B cell malignancies enabled by Interius’s programmable platform. In our preclinical studies, we achieved successful B cell depletion in small and large animal models without chemotherapy and observed no signs of cytokine release syndrome (CRS) or neurotoxicity. We look forward to sharing interim clinical safety and proof-of-concept data at a scientific meeting next year."

Dr. Michael Dickinson, MBBS, FRACP, Lead of the Aggressive Lymphoma Disease Group at Peter MacCallum Cancer Centre and Royal Melbourne Hospital and INVISE Principal Investigator, added, "The need for new, accessible treatment options for patients with cancer is critical. Innovative approaches, like in vivo CAR gene therapies, have the potential to transform how we treat cancer, offering faster, single-dose solutions that are less burdensome on patients and treatment centres."

About INVISE
INVISE (INjectable Vectors for In Situ Engineering) is a first-in-human Phase 1 clinical trial evaluating the safety of INT2104 intravenous infusion in adults with refractory/relapsing B cell malignancies. The study is a global, two-part, multicenter, open-label, single dose design with a dose escalation portion designed to inform the dose of INT2104 to be used in the dose confirmation part of the trial and future studies. INVISE has been granted Human Research Ethics Committee (HREC) approval and Clinical Trial Notification (CTN) clearance by the Australian Therapeutic Goods Administration (TGA). Additional information and enrollment criteria may be found on clinicaltrials.gov (NCT06539338).

About INT2104
INT2104 is a wholly-owned investigational gene therapy candidate, which specifically targets CD7-positive T and NK cells and delivers a CAR transgene to create effector CAR-T and CAR-NK cells in vivo. The CAR cells target CD20-positive B cells for the treatment of B cell malignancies. Unlike ex vivo CAR-T therapies, INT2104 is an off-the-shelf, single dose treatment, administered systemically through intravenous infusion without the need for lymphodepletion or for any special equipment or training.