On December 6, 2022 RemedyBio, a Dublin based biotech company, inspired by functional biology for the discovery and development of new immune therapies using the power of its Nanoreactor Technology for the analysis of individual cells and cell interactions, reported their participation in INSPIRE, a €12.8 million lung cancer program (Press release, Remedy Biologics, DEC 6, 2022, View Source [SID1234644158]). In one of the largest ever grants for preclinical research in lung cancer, RemedyBio will collaborate with programme leader, OmniSpirant and other European partners spanning across biotechnology, medical devices, cancer research, academia and patient advocacy.

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!

With the successful award of the grant by Horizon Europe, the INSPIRE consortium are already actively working on the program deliverables, and recently met in Galway, Ireland for the official kick off meeting. As well as OmniSpirant and RemedyBio, the consortium partners include Aerogen Limited (Ireland), Trinity College Dublin (Ireland), EVerZom (France), Biopharma Excellence (Pharmalex) (Germany), Deutsches Krebsforschungszentrum (DKFZ) (Germany) and Lung Cancer Europe (LuCE) (Switzerland).
Over the next 3 years, the INSPIRE programme aims to make an important and tangible impact on Europe’s Beating Cancer Plan and the EU Mission on Cancer. The consortium partners will work to develop a novel, effective and affordable lung cancer treatment via the development of a transformative new lower cost gene therapy. This project will place Europe as a leader in the fight against lung cancer and in the development of treatments for other debilitating lung diseases.
RemedyBio’s key role in the programme will be based on using RemedyBio’s proprietary Nanoreactor technology to investigate functional cell to cell interactions between the tumour and the gene therapy, building understanding of the efficacy of the new therapy.
"We are delighted to be part of the INSPIRE consortium in order to develop new and more effective therapies that impact patients lives", said Dan Crowley, CEO of Remedy Bio. "Our Nanoreactor technology and understanding of cell to cell interaction with help to drive insight and direction with our consortium partners in developing new RNA based therapeutics for lung cancer."

On December 6, 2022-Defence Therapeutics Inc. ("Defence" or the "Company"), a Canadian biopharmaceutical company specialized in the development of immuneoncology vaccines and drug delivery technologies, reported the successful completion of all GLP studies related to its anti-cancer AccuTOXTM molecule (Press release, Defence Therapeutics, DEC 6, 2022, View Source [SID1234626257]). The Company is planning to meet with the FDA in the weeks to come to obtain approval for launching its Phase I trial against solid tumors.

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!

AccuTOXTM: a fierce anti-cancer treatment.

In the past 16 months, Defence engineered a large library of AccumTM variants exhibiting differential effects on both immune and cancer cells. One of these lead molecules is AccuTOXTM, a small compound capable of effectively killing a large set of murine and human tumors by inducing the production of reactive oxygen species, causing immunogenic cells death as well as triggering direct DNA damage akin to chemotherapeutic agents. Interestingly, AccuTOXTM administration synergises with different immune-checkpoints (anti-PD-1, anti-CTLA4 and antiCD47) making it a highly mouldable molecule adaptable to a myriad of solid cancer indications. For instance, AccuTOXTM dosed at 16 mg/kg halts the growth of solid T-cell lymphoma, melanoma as well as breast cancer in mice with a survival rate of more than 90%. These results combined to the molecular characterization of AccuTOXTM’s mechanism of action clearly highlight the anti-neoplastic potential of this molecule as a next generation treatment for various cancer types.

GLP studies in rodents revealed no adverse effects for AccuTOXTM.

Building upon the impressive results obtained in different pre-clinical murine cancer models, a set of GLP studies was then conducted in male and female Sprague-Dawley rats to determine the toxicity potential and toxicokinetic profile of AccuTOXTM when administered through the subcutaneous route for 14 days (delivered every 48h for a total of 7 repetitive injections). Besides slight erythema/edema at the injection site, no clinical signs of morbidity or mortality were observed in both sexes using a dose as high as 30 mg/kg, which is twice as high as the therapeutic dose used in pre-clinical studies. Animals body weight, food consumption, coagulation and urine parameters were unaffected at all tested doses in both male and female rates. Hematological changes were considered minimal with no noticeable side effects to report. Furthermore, the time to reach peak plasma concentration (Tmax) was ~1h in both genders. In conclusion, AccuTOXTM exhibits no adverse effects in rats and is well tolerated even at repetitive dosing of 30 mg/kg.

AccuTOXTM is safe and well tolerated in canines.

Upon completing the GLP study in rats, Defence followed up with a second set of GLP studies in Beagle dogs. In this case, higher AccuTOXTM doses were used (up to 100 mg/kg, which is 6.2-fold higher than the therapeutic dose used in mice). Although no clinical signs were observed up to 50 mg/kg, a very slight erythema was observed at the injection site following single dosing. Repetitive dosing, on the other hand, revealed very limited erythema and hardness at injection sites, which were considered of minimal impact. No mortalities were observed in male or female dogs up to 100 mg/kg and body weights of all treated animals were consistent despite a small decrease in food consumption. No apparent changes were noticed in the conducted electrocardiograms in both genders nor in their hematological, coagulation and urinalysis parameters. Chronic inflammation was apparent at the injection sites associated with mild leukocyte infiltration. The Tmax for AccuTOX in dogs varied between 0.25 and 1h in both genders, with a detected T1/2 of ~0.553h. In sum, AccuTOXTM is safe and well tolerated by Beagles with limited local effects observed at injection sites.

A Phase I trial in the pipeline

"The AccuTOXTM program has greatly matured since its inception in mid-2021. The molecule is highly effective as an anti-cancer molecule and exhibits no toxic effects in different animal models (mice, rats and dogs). The fact that dogs can tolerate AccuTOXTM up to 100 mg/kg demonstrates a larger than expected therapeutic window for this treatment", says Mr. Plouffe, the CEO of Defence Therapeutics. Defence is currently preparing to meet with the FDA in the up-coming weeks to present its preclinical and GLP studies to get approval for initiating a Phase I trial on a basket of solid tumors. The primary objective will be to demonstrate the safety and tolerability of the drug in cancer patients, while assessing some form of potency as secondary objective. Data Bridge Market Research analyses that the solid tumors market was valued at USD 209.61 billion in 2021 and is expected to reach USD 901.27 billion by 2029, registering a CAGR of 20.0% during the forecast period of 2022 to 2029.

On December 6, 2022 Achilles Therapeutics plc (NASDAQ: ACHL), a clinical-stage biopharmaceutical company developing AI-powered precision T cell therapies to treat solid tumors, reported an encouraging interim Phase I/IIa update on the use of clonal neoantigen reactive T cells (cNeT) from the CHIRON study in advanced unresectable or metastatic non-small cell lung cancer (NSCLC) and the THETIS study in recurrent or metastatic malignant melanoma at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2022 (ESMO IO) (Press release, Achilles Therapeutics, DEC 6, 2022, View Source [SID1234625326]).

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 early safety, tolerability, and durable clinical benefit in heavily pre-treated patients presented today are encouraging and illustrate the promising therapeutic potential of cNeT monotherapy. Further, the strength of our translational science platform was shown by our ability to track key elements of activity that correlated to cNeT presence," said Dr Iraj Ali, CEO of Achilles Therapeutics. "We look forward to providing further updates in 2023, including additional monotherapy data from CHIRON and THETIS, and initial THETIS combination data evaluating cNeT with a PD-1 checkpoint inhibitor."

"The partial response and stable disease observed with low doses of cNeT in this difficult to treat patient population are encouraging, and coupled with the well-tolerated safety profile, highlight a favorable therapeutic window to further dose escalate and help drive deeper, more durable responses," added Dr. Karl Peggs, Chief Medical Officer of Achilles Therapeutics. "We believe this is the first time a response in lung cancer has been demonstrated using a cell therapy with a low dose conditioning and IL-2 regimen, which importantly, could expand eligibility of this therapy to include patients with comorbidities or reduced fitness that may not be candidates for traditional TIL therapy."

Dr. Sergio Quezada, Chief Scientific Officer of Achilles Therapeutics added, "In addition to the durable clinical benefit, our translational science platform begins to deliver key mechanistic insights for our cNeT therapy that are not possible with a standard TIL product, including assessment of phenotypic markers as well as proliferative and cytolytic capacity of the tumor reactive cNeT component. By virtue of knowing the cNeT targets and being able to characterize and track specific cNeT in the product and in the blood of patients, we can monitor cNeT dose, markers of function and exhaustion, engraftment, activation, and other features related to the patient, product, and performance in vivo."

Early, encouraging proof-of-concept data support the potential of cNeT monotherapy to deliver durable clinical benefit
14 patients treated (8 NSCLC in CHIRON, 6 melanoma in THETIS) with median of two prior lines of therapy
Two additional patients dosed since ESMO (Free ESMO Whitepaper) IO cut-off: one in CHIRON and one in THETIS Cohort B (checkpoint combination)
Confirmed partial response and stable disease achieved with low doses of cNeT and reduced dose lymphodepletion and IL-2 in NSCLC
1 partial response (PR, 56% tumor reduction maintained at week 36) and 6 patients with stable disease (SD) with overall durable clinical benefit at 12 weeks in 71% of evaluable patients (5/7) with advanced NSCLC
cNeT driven anti-tumor activity in the partial responder is supported by T cell engraftment and cytokine profiles
Stable disease in 50% of evaluable patients (3/6) with melanoma
cNeT product characterization supports a polyfunctional active component
Encouraging early safety and tolerability profile for cNeT
Safety and tolerability observations of cNeT compare favorably to standard tumor infiltrating lymphocytes (TIL) due to less IL-2 related toxicity
Lymphopenia and neutropenia were the most common adverse events, which are principally associated with the conditioning regimen, and no dose limiting high-grade toxicities associated with IL-2 were reported
Reduced dose lymphodepletion and IL-2 may expand patient eligibility criteria to include those with greater co-morbidities
Robust translational science platform correlates cNeT to activity
cNeT display an activated and functional phenotype including markers associated with tissue migration and a transcriptional profile supporting proliferation and cytotoxic function
Effective lymphodepletion and subsequent immune reconstitution were observed in all patients despite lower doses of lymphodepleting agents
Functional activity of cNeT supported by the observation of peak expansion of cytokine-secreting cNeT 21 days post infusion, coinciding with a peak in IL-6, with detection of cNeT beyond 12 weeks by TCR analysis
Manufacturing process evolution continues to increase cNeT doses
78 million median cNeT dose of first Process 2 products (n=3, CHIRON), with median 17% reactivity
47 million median cNeT dose across patient products since last update vs. 14 million in the first eight patients reported at SITC (Free SITC Whitepaper) 2021

Webcast and Conference Call Details

The company will host a live webcast and conference call today, Tuesday, December 6, 2022 at 8:00am ET / 1:00pm UK to review the interim update presented at ESMO (Free ESMO Whitepaper) IO. The live conference call will be webcast in listen-only mode and a slide presentation will be made available in the Events & Presentations section of the Company website at View Source For listeners who wish to participate in the question-and-answer session via telephone, please pre-register here.

On December 6, 2022, HCW Biologics Inc. was granted U.S. Patent No. 11,518,792 by the United States Patent and Trademark Office which contains claims for construction of novel multi-function fusion immunotherapeutic compounds comprised of a multi-chain chimeric polypeptide where the first target-binding domain and the second target-binding domain is a soluble human transforming growth factor-β ("TGF-β") receptor (Press release, HCW Biologics, DEC 6, 2022, View Source [SID1234624894]).

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!

This patent provides intellectual property protection for the Company’s lead drug candidate, HCW9218, a heterodimeric, bifunctional fusion protein complex comprising extracellular domains of human tissue factor as a scaffold with target binding domains of TGF-β receptor II, as a TGF-β trap for TGF-β neutralization, and a human interleukin ("IL")-15/IL-15 receptor α complex for immune cell stimulation.

On December 6, 2022 OmniSpirant Limited and EVerZom are delighted to announce the launch of INSPIRE, a €12.8 million lung cancer project funded by Horizon Europe (Press release, OmniSpirant, DEC 6, 2022, View Source [SID1234624871]). The project gathers European partners spanning across biotechnology, medical devices, cancer research, academia and patient advocacy including Aerogen Limited (Ireland), Trinity College Dublin (Ireland), RemedyBio (Ireland), Myriad Associates (Ireland), EVerZom (France), Biopharma Excellence (Pharmalex) (Germany), Deutsches Krebsforschungszentrum (DKFZ) (Germany) and Lung Cancer Europe (Switzerland). Over the next 3 years of the project, this world-class consortium will progress the development of a regenerative gene therapy as a transformative new treatment for lung cancer. The INSPIRE programme aims to make an important and tangible impact on Europe’s Beating Cancer Plan and the EU Mission on Cancer.

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!

Lung cancer presents a significant health policy challenge with over 470 thousand cases reported annually in Europe, accounting for 11% of all cancers and 15% of healthcare expenses in cancer. The state-of-the-art approved treatments, such as targeted therapy and immune checkpoint inhibitors are prone to treatment resistance. The overall 5-year survival rates for people with lung cancer remain extremely poor, highlighting the desperate need for innovative treatments.

OmniSpirant is an Irish biotech founded in 2016 to develop first-in-class inhaled regenerative gene therapies. This development is based on its proprietary OmniSome platform technology, which utilises tiny particles carrying cellular cargoes, known as extracellular vesicles (EVs) secreted by stem cells. Targeted indications are pulmonary diseases like cystic fibrosis or alpha-1 antitrypsin deficiency (AATD), and now, lung cancer via the INSPIRE project.

"We are delighted to collaborate with our pan-European partners in developing this exciting new approach" said OmniSpirant CEO Gerry McCauley. "We are at the forefront of harnessing extracellular vesicles to deliver RNA based therapeutics in the fight against lung cancer and in developing our platform to address a host of chronic pulmonary conditions"

"We are delighted to collaborate with OmniSpirant to bring our technologies and know how to manufacture extracellular vesicles at large scale and affordable costs to develop this future breakthrough treatment." said Jeanne Volatron, EVerZom CEO.

For more information, please visit inspire.lungcancereurope.eu and www.omnispirant.com or contact Gerry McCauley, CEO at [email protected] or Jeanne Volatron, CEO at [email protected]