On November 1, 2023 AstraZeneca reported a collaboration and investment agreement with Cellectis, a clinical-stage biotechnology company, to accelerate the development of next generation therapeutics in areas of high unmet need, including oncology, immunology and rare diseases (Press release, AstraZeneca, NOV 1, 2023, View Source [SID1234636568]).

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Under the terms of the collaboration agreement, AstraZeneca will leverage the Cellectis proprietary gene editing technologies and manufacturing capabilities, to design novel cell and gene therapy products, strengthening AstraZeneca’s growing offering in this space. As part of the agreement, 25 genetic targets have been exclusively reserved for AstraZeneca, from which up to 10 candidate products could be explored for development.

Marc Dunoyer, Chief Strategy Officer, AstraZeneca, and Chief Executive Officer, Alexion, AstraZeneca Rare Disease, said: "The differentiated capabilities Cellectis has in gene editing and manufacturing complement our in-house expertise and investments made in the past year. AstraZeneca continues to advance our ambition in cell therapy for oncology and autoimmune diseases as well as in genomic medicine, which has potential to be transformative for patients with rare diseases."

André Choulika, PhD, Chief Executive Officer of Cellectis, said: "We believe AstraZeneca is the perfect match to Cellectis by providing world-class expertise in the development and the commercialisation of innovative medicines. This collaboration will allow us to leverage our pioneering research in gene editing and cell therapies, as well as our cutting-edge capabilities in manufacturing with the ambition to bring potentially life-saving therapies to patients with unmet medical need."

Building on AstraZeneca’s own expertise in cell and genomic therapy, the Company has enhanced its capabilities through several collaborations and investments in the past year as part of its ambition to bring cell therapies to more patients living with cancer and to advance genomic medicines for rare diseases.

Financial considerations
In Q4 2023, Cellectis will receive an initial payment of $105m from AstraZeneca, which comprises a $25m upfront cash payment under the terms of a research collaboration agreement and an $80m equity investment.

The initial equity investment of $80m, at $5/share, represents an equity stake of c. 22% in Cellectis. A further $140m equity investment, at $5/share, is expected to close in early 2024 subject to the signing of a final binding agreement following completion of a consultation with the Cellectis employee representative bodies and customary closing conditions including Cellectis shareholders’ approval and regulatory clearances. Post-closing of this second investment, AstraZeneca will hold a total equity stake of c. 44% in Cellectis. AstraZeneca expects to treat its investment in Cellectis as an associate.

Under the terms of the research collaboration, Cellectis is also eligible to receive an investigational new drug (IND) option fee and development, regulatory and sales-related milestone payments, ranging from $70m up to $220m, per each of the 10 candidate products, plus tiered royalties.

AstraZeneca retains an option for a worldwide exclusive license for the candidate products developed under the research collaboration agreement, to be exercised before IND filing.

On October 31, 2023 Lirum Therapeutics, Inc. ("Lirum"), an innovative clinical-stage biopharmaceutical company focused on the treatment of debilitating diseases, reported the presentation of positive data at the 2023 Connective Tissue Oncology Society meeting in Dublin, Ireland (Press release, Lirum Therapeutics, OCT 31, 2023, View Source [SID1234651603]).

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LX-101, a novel clinical-stage payload-bearing targeted therapy directed to the insulin-like growth factor 1 receptor (IGF-1R),demonstrated potent anti-tumor activity against cell lines with well-established IGF-1R pathway involvement, including pediatric sarcomas. These include cancers with known genetic alterations affecting the IGF-1R pathway and/or with high IGF-1R expression such as Ewing’s and related sarcomas, rhabdomyosarcoma, and osteosarcoma.

LX-101 was active against a variety of pediatric cancer cell lines including Ewing’s sarcoma (with EWSR1-FLI1 and EWSR1-ERG gene fusions), alveolar rhabdomyosarcoma (with the PAX3-FOXO1 gene fusion), and osteosarcoma. The poster will be presented on November 2, 2023 at 5:30 PM IST (local time) and will be available on the Lirum website (www.lirumtx.com) under the Investors and Media tab.

Given these promising results, and the existing clinical data, Lirum is planning new clinical trials with LX-101 in pediatric and adult oncologic indications that carry strong ties to the IGF-1/IGF-1R pathway. In parallel, Lirum is also planning to develop LX-101 in certain autoimmune diseases, such as thyroid eye disease (TED), where IGF-1R has been clinically and commercially validated.

About LX-101

Lirum’s lead product candidate, LX-101, is a novel, clinical-stage, next generation, precision-engineered, payload-bearing targeted therapy directed to the insulin-like growth factor 1 receptor (IGF-1R). The IGF-1/IGF-1R pathway has been implicated in a host of malignancies and autoimmune diseases, including thyroid eye disease (TED), and which Lirum believes represents a scientifically and medically rational target in both oncology and autoimmune indications. LX-101 consists of a proprietary, engineered variant of the IGF-1 ligand, conjugated to a cytotoxic payload, methotrexate, and harbors a novel and differentiated mechanism of action versus current and past IGF-1R targeted approaches.

LX-101 (formerly 765IGF-MTX) has been evaluated in Phase 1 clinical trials of patients with advanced, pretreated solid and hematologic cancers. It was found to be well-tolerated and demonstrated single agent activity. No dose limiting toxicity or maximum tolerated dose were reached, and Lirum intends to explore further dose escalation and schedule optimization as well as focus on those indications with strong ties to the IGF-1/IGF-1R pathway.

On October 31, 2023 iOnctura, a clinical-stage biotech developing selective cancer therapies against targets that play critical roles in multiple tumor survival pathways, reported that the US Food and Drug Administration (FDA) has granted permission to proceed with clinical investigations of roginolisib in the United States of America (Press release, iOnctura, OCT 31, 2023, View Source [SID1234640231]).

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Roginolisib (IOA-244) is in development for solid and hematologic malignancies including uveal melanoma, a rare cancer in which malignant (cancer) cells form in the uveal tract of the eye. When the cancer metastases, which it does in approximately 50% of patients, there are limited treatment options and projected overall survival is only a year.

As the first novel allosteric modulator of PI3Kδ, roginolisib marks a new era in drug development within the class. The unique binding mode, combined with high selectivity for PI3Kδ, is expected to translate to an improved safety and tolerability profile relative to that of earlier generation inhibitors.

"As we remain on track to deliver final clinical data from the initial patients treated with roginolisib in 2024, the clearance of our IND application demonstrates our commitment to driving roginolisib through the clinic" said Catherine Pickering, Chief Executive Officer of iOnctura. "We believe roginolisib has the potential to slow or halt the progression of uveal melanoma, so providing an important treatment option for patients who currently have no approved therapeutic options after they progress on their first line therapy."

Roginolisib is being investigated in the DIONE-01 trial, a two-part, first-in-human Phase I study (ClinicalTrials.gov, identifier NCT04328844). The study is fully enrolled with final data expected Q1 2024. Across all patients treated to date, roginolisib monotherapy has shown 7% Grade 3/4 toxicities, with no dose limiting toxicities, drug-related serious adverse event (SAE) or drug related adverse event (AE) leading to dose interruption or discontinuation. Whilst median Overall Survival has not yet been reached, 62% of patients were alive at 12 months, which compares favourably to historical controls of 34% in the same setting[1].

Long-term administration of roginolisib is well tolerated and patients have been treated for up to 40 months in the study. Promising clinical activity has been observed across patients with both solid and hematological cancers.

[1] Rantala et al., Melanoma Res. 2019 Dec;29(6):561-568

On October 31, 2023 Molecure S.A. ("Molecure": WSE: MOC) a clinical stage biotechnology company developing first-in-class small molecule drug candidates that directly modulate unexplored protein and RNA targets to treat multiple incurable diseases reported third quarter results for the period ended 30 September 2023 (Press release, Molecure, OCT 31, 2023, View Source [SID1234640059]). The full report in Polish can be found here View Source

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Marcin Szumowski, CEO and President of the Management Board of Molecure said: "We have made substantial financial and operational progress during 2023 including the completion of a significantly oversubscribed secondary public offering. This will enable the company to deliver meaningful additional data which will be important in fulfilling the longer-term potential of our pipeline.

We have also achieved key milestones in clinical development with the dosing of the first cancer patient in our Phase I study with OATD-02 with anticipated initial results in the next few months. Additionally, we expect to dose the first pulmonary sarcoidosis patient in the Phase II study of OATD-01 before the end of the year.

Molecure is entering a very exciting stage in its development with a number of near-term value-creating milestones set to be achieved in our pipeline and we look forward to providing meaningful updates on our progress over the next year. "

Commercial & Operational Highlights in the third quarter

Successful Public Offering

Molecure successfully raised, through a Secondary Public Offering, gross proceeds of approximately PLN50m (USD12m) from existing and new shareholders,
Proceeds and expected grant awards will be used to fund and build Molecure’s first in class sustainable pipeline of breakthrough therapies through significant value inflection points including completion of the Phase II study for OATD-01 in sarcoidosis and completion of the Phase I clinical trial for OATD-02 in oncology patients, with the possibility of expansion into additional indications and combination therapies.
US FDA Clearance to conduct Phase II clinical trial – OATD-01

Molecure received US FDA Investigational New Drug (IND) approval for OATD-01 which will allow the company to conduct Phase II clinical trials in the US. The planned Phase II proof-of-concept study will be the first to treat patients suffering from pulmonary sarcoidosis and is expected to start in the fourth quarter 2023.
Molecure has submitted applications to the EMA and UK MHRA to initiate a Phase II clinical trial in the European Union and Norway and the UK respectively.
Molecure signed an agreement with Simbec-Orion, a leading global Clinical Research Organization which will conduct the clinical trial on behalf of Molecure. The Phase II trial will be conducted in the US and several European Union Countries and enroll 90+ patients with active pulmonary sarcoidosis.
Nine Months Financial Highlights

Operating income of PLN1.3 million, in line with the same period in 2022.
Operating expenses totaled PLN16.3 million, an increase of PLN4.3 million vs the same period last year. This was mainly due to higher research costs as the company’s pipeline advances, higher salaries and costs of external services.
Net loss for the first nine months of the year totaled PLN11.5 million vs net loss of PLN9.4 million in the first nine months of the year in 2022.
As of September 30, 2023, Molecure had cash of nearly PLN85 million (US$20 million).
US$/PLN exchange rate 4.2 as of 30 September 2023.

On October 31, 2023 Incyte reported its 2023 third quarter financial and corporate update (Presentation, Incyte, OCT 31, 2023, View Source [SID1234639530]).

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