On June 6, 2023 Almac Discovery, the drug discovery biotech operating within the Almac Group of companies, reported that the highly selective WEE1 inhibitor which it licensed to Debiopharm (Switzerland) and now known as Debio 0123, has been progressed into further clinical studies (Press release, Almac, JUN 6, 2023, View Source [SID1234632506]). The first patients have now received treatment in two separate clinical studies involving glioblastoma (GBM) and small cell lung cancer (SCLC).

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In both studies, Debiopharm has combined Debio 0123 with standard of care therapy in patients with either GBM, one of the most aggressive and common lethal tumours of the central nervous system, or SCLC, a highly aggressive, hard-to-treat cancer with poor prognosis.

The Debio 0123 programme offers the potential to improve clinical outcomes and quality of life for patients suffering from GBM or SCLC. In cancer cells, DDR pathways are often upregulated due to genomic instability, providing potential resistance pathways to DNA-damaging therapies. Therefore, blocking kinases such as WEE1 which play essential roles in DNA repair is likely to increase the cancer’s vulnerability to SOC therapies. Preclinical results have shown that Debio 0123 successfully crosses the blood brain barrier and inhibits tumour growth.

Dr Stephen Barr, Managing Director and President, Almac Discovery said: "Since the discovery of our highly selective WEE1 inhibitor, we have looked forward to understanding its potential therapeutic benefit for cancer patients across the globe. We are delighted that it has progressed into further clinical development in these two cancer indication studies with high unmet medical need and look forward to seeing further progress from this ongoing clinical research."

"The Debio 0123 program originates from a growing awareness of DDR inhibition in fighting life-threatening cancers. Optimizing efficacy, while preserving safety are key elements that Debiopharm is eager to assess throughout the clinical development of Debio 0123. With the fruition of these factors, Debio 0123 could become the first choice WEE1 inhibitor." Angela Zubel, Chief Development Officer, Debiopharm.

On June 6, 2023 AbbVie (NYSE: ABBV) reported that it will participate in the Goldman Sachs 44th Annual Global Healthcare Conference on Wednesday, June 14, 2023 (Press release, AbbVie, JUN 6, 2023, View Source [SID1234632505]). Robert A. Michael, vice chairman and president, Jeffrey R. Stewart, executive vice president, chief commercial officer and Roopal Thakkar, senior vice president, development and regulatory affairs and chief medical officer, will present at 10:00 a.m. Central time.

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A live audio webcast of the presentation will be accessible through AbbVie’s Investor Relations website at investors.abbvie.com. An archived edition of the session will be available later that day.

On June 5, 2023 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, reported an equity investment round of €255 million led by Temasek with participation from BlackRock Alternatives1, Qatar Investment Authority (QIA), Nextech2, ATHOS and Carbyne. The round comprised mostly of primary capital alongside a minority transaction of secondary shares. Primary net proceeds to the company will support further development of ITM’s broad Targeted Radionuclide Therapies (TRT) oncology pipeline and enhance commercial readiness as the company nears the final stages of phase III clinical development for its lead pipeline candidate, ITM-11 (n.c.a. 177Lu-edotreotide) in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In addition, the company will expand its market-leading manufacturing capacities and infrastructure for n.c.a. 177Lu, scale GMP-manufacturing for 225Ac, and expand in-house drug product manufacturing capabilities to accelerate the global access to radiopharmaceuticals worldwide.

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Since its inception, ITM has made substantial progress in delivering on its ambitious corporate and clinical goals:

Advancing lead drug candidate ITM-11 into two phase III clinical trials for GEP-NETs and ITM-31 (Lu-177 labeled 6A10 Fab-fragments) into clinical studies for glioblastoma. Full details of ITM’s pipeline are described at View Source;
Expanding production capacity by building a second state-of-the-art manufacturing facility in Germany equipped with the full spectrum of capabilities to manufacture multiple radioisotopes and radiotherapies at scale – to be opened soon;
Opening the U.S. Headquarters in Princeton, New Jersey; and
Establishing a subsidiary in Shanghai, China to accelerate introduction of precision oncology products in the region.
"ITM is a leading radiopharmaceutical company with an advanced proprietary pipeline and has established itself as the major radioisotope supplier globally. This financing supports our objective to serve a broad patient population by ensuring a consistent supply of radionuclides and radiopharmaceuticals to meet the growing demand of medical professionals and our partners across the pharmaceutical, healthcare and research sectors globally," commented Udo J. Vetter, Chairman of the Supervisory Board at ITM.

"Securing one of the largest private biotechnology financing rounds ever in our home market from major, globally active investors with deep biotech experience underscores our presence at the forefront of the radiopharmaceutical space on an international scale," added Steffen Schuster, CEO of ITM. "As we near the final stages of clinical development for ITM-11 in GEP-NETs, this substantial investment will help to further grow our supply network and accelerate our efforts to bring new, targeted treatments to patients living with hard-to-treat cancers."

ITM also announced that Petrichor’s €90 million convertible loan was converted into equity per the terms of that initial agreement.

(Press release, ITM Isotopen Technologien Munchen, JUN 5, 2023, View Source,_Plans_to_Advance_Radiopharmaceutical_Pipeline_and_to_Expand_Radioisotope_Production_Capacities-643/ [SID1234661155])

On June 5, 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 7th Cancer World Congress in Palermo, Italy (Press release, Lirum Therapeutics, JUN 5, 2023, View Source [SID1234651602]).

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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 of pediatric cancers with well-established IGF-1/IGF-1R pathway involvement. These include cancers with known genetic alterations affecting the IGF-1/IGF-1R pathway and/or with high IGF-1R expression such as Ewing’s and related sarcomas, rhabdomyosarcoma, osteosarcoma, and neuroblastoma.

LX-101 was active, with IC50s ranging from 6 nM to 33 nM, 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), osteosarcoma, and neuroblastoma. The audio poster presentation from the conference is 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 these indications that carry strong ties to the IGF-1/IGF-1R pathway. In parallel, Lirum is also planning to develop LX-101 in IGF-1/IGF-1R-involved adult cancers as well as certain autoimmune diseases, including 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 June 5, 2023 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported promising preliminary Phase 1b data for ERK inhibitor ERAS-007 in patients with metastatic BRAF V600E-mutated (BRAFm) colorectal cancer (CRC) and provided a portfolio update (Press release, Erasca, JUN 5, 2023, View Source [SID1234639354]). Erasca will host a virtual investor event to discuss these updates today at 4:30 PM ET. To register for the event, please click here.

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"We are pleased that the early ERAS-007 clinical data continue to reinforce its potential to become a backbone for combination therapy," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "Moreover, through our signal-seeking trials, we have tested three biological hypotheses: preventing in-pathway resistance, reversing in-pathway resistance, and targeting adjacent pathways. We believe the encouraging efficacy data for ERAS-007 in combination with encorafenib and cetuximab in EC-naïve patients with BRAFm CRC (preventing in-pathway resistance) provide compelling evidence to continue with further enrollment in this patient population."

Dr. Lim continued, "Due to a lack of clinical activity, we will not continue exploring ERAS-007 combined with palbociclib in patients with RAS-mutated gastrointestinal malignancies (targeting adjacent pathways) or ERAS-007 combined with osimertinib in patients with post-osimertinib EGFR-mutated non-small cell lung cancer (reversing in-pathway resistance). We have also decided to deprioritize certain discovery programs: ERAS-9 (SOS1), ERAS-11 (MYC), and ERAS-2/3 (RAS switch-II groove targeting), but are pursuing other promising research approaches to target RAS mutations beyond G12C. Further refining our efforts and prioritizing resources will allow us to focus on clinical and research programs with potential therapeutic differentiation and will increase our capacity to realize the many exciting opportunities ahead of us to help patients. We continue to be well positioned to execute on important catalysts over the next 18 months and beyond for our four clinical programs, our pan-RAF inhibitor naporafenib, ERK inhibitor ERAS-007, SHP2 inhibitor ERAS-601, and CNS-penetrant EGFR inhibitor ERAS-801."

ERAS-007 Development Update
Meaningful activity in patients with EC-naïve BRAFm CRC supports initial focus on and dose expansion of this patient population*:

50% (3/6) response rate, including two confirmed partial responses (cPR) and one unconfirmed partial response (uPR), and 67% (4/6) disease control rate (DCR; defined as complete response + partial response + stable disease) in EC-naïve response evaluable patients at the highest dose of ERAS-007 tested (100 mg BID-QW), with duration of exposure for both cPRs >40 weeks as of the data cutoff date; across all dose levels in EC-naïve response evaluable patients, 38% (3/8) response rate, including two cPRs and one uPR, and 63% (5/8) DCR. Per site communication, the patient with the uPR was still in response at the subsequent scan (May 26, 2023), which was conducted 25 days after the first post-baseline scan
ERAS-007 + EC was generally well tolerated with mostly low-grade treatment-related adverse events (TRAEs) at all combination doses tested. No Grade 4 or 5 TRAEs were observed
One dose-limiting toxicity (DLT) was reported for ERAS-007 100 mg BID-QW + EC (Grade 3 macular edema)
Pharmacokinetic (PK) exposures of ERAS-007, encorafenib, and cetuximab were comparable to the respective monotherapy PK data, suggesting no apparent PK drug-drug interactions (DDI) between the study drugs
* Safety data cutoff date was March 23, 2023. Efficacy data cutoff date was May 21, 2023

Across the HERKULES studies, early clinical data reinforce ERAS-007’s potential to be a backbone for combination therapy:

Target PK profile achieved with adequate exposures and well-defined PK in monotherapy and combinations
No apparent PK DDI liabilities were observed for ERAS-007 when dosed in combination with multiple approved therapies
ERAS-007 has been safely combined with other agents at biologically relevant doses and schedules
ERAS-007 monotherapy responses observed in multiple tumor types support further evaluation of intermittent scheduling in combination
Encouraging signs of efficacy for select ERAS-007 combinations
Portfolio Update
A data-driven prioritization focuses Erasca’s resources on opportunities with the highest probability of success for patients.

Development Programs

HERKULES-3: ERAS-007 + EC in EC-naïve patients with BRAFm CRC (preventing in-pathway resistance): Conducting dose expansion based on encouraging early efficacy data in EC-naïve patients
HERKULES-3: ERAS-007 + EC in EC-treated patients with BRAFm CRC (reversing in-pathway resistance): Gating evaluation on efficacy data in EC-naïve CRC population (i.e., EC-treated population may be explored if efficacy data continue to be promising in the EC-naïve population), as it is more challenging to show treatment benefit in EC-treated population than in EC-naïve population
HERKULES-2: ERAS-007 + osimertinib in patients with post-osimertinib EGFR-mutant NSCLC (reversing in-pathway resistance): Deprioritized as clinical efficacy data do not support continued evaluation
HERKULES-3: ERAS-007 + palbociclib in patients with KRAS- or NRAS-mutant CRC and KRAS-mutant PDAC (targeting adjacent pathways): Deprioritized as clinical efficacy data do not support continued evaluation
HERKULES-1: ERAS-007 + ERAS-601 in patients with advanced solid tumors: Deprioritized as dose escalation safety data do not support continued evaluation of regimen tested
AURORAS-1: ERAS-3490 in patients with KRAS G12C-mutated solid tumors: Deprioritized due to increasingly competitive landscape for small- and mid-cap biopharma companies despite the program’s potential differentiation
Research Programs

ERAS-9 SOS1: Deprioritized to focus on SHP2 as the key upstream RAS/MAPK pathway node due to promise of ERAS-601 SHP2 inhibitor
ERAS-11 MYC: Deprioritized as preclinical characterization does not support continued work
ERAS-2/3 RAS Switch-II Groove targeting: Deprioritized and pursuing other promising research approaches to target RAS mutations beyond G12C
Key Upcoming Milestones
Erasca re-affirmed its prior guidance for the following, with respect to anticipated key milestones and clinical trial readouts:

Naporafenib (pan-RAF inhibitor)
SEACRAFT-1: Phase 1b trial for naporafenib plus trametinib in patients with RAS Q61X solid tumors
First patient dosing expected in second half of 2023
Initial Phase 1b combination signal-seeking efficacy data in relevant tumor types expected between the second and fourth quarters of 2024
SEACRAFT-2: Randomized pivotal Phase 3 trial for naporafenib plus trametinib in patients with NRASm melanoma
First patient dosing expected in first half of 2024
ERAS-007 (ERK1/2 inhibitor)
HERKULES-3: Phase 1b trial for ERAS-007 plus EC in EC-naïve BRAFm CRC patients
Phase 1b combination expansion data in patients with BRAFm CRC expected between the second half of 2023 and the first half of 2024
ERAS-601 (SHP2 inhibitor)
FLAGSHP-1: Phase 1b trial in patients with advanced solid tumors
Phase 1b combination expansion data in relevant patient populations, including patients with human papillomavirus (HPV)-negative advanced head and neck squamous cell carcinoma (HNSCC) expected in first half of 2024
ERAS-801 (CNS-penetrant EGFR inhibitor)
THUNDERBBOLT-1: Phase 1 trial in patients with recurrent glioblastoma (GBM)
Initial Phase 1 monotherapy dose escalation data in patients with recurrent GBM expected in second half of 2023