On September 12, 2022 Transgene (Euronext Paris: TNG) (Paris:TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, reported that positive confirmatory data from the Phase I trial evaluating TG6002 administered intravenously (IV) in combination with oral 5-FC in patients with advanced gastrointestinal carcinomas (Press release, Transgene, SEP 12, 2022, View Source [SID1234619442]).

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TG6002 is based on Transgene’s double deleted VVcopTK-RR- patented virus backbone, which forms the basis of the company’s Invir.IO platform, and is generating a pipeline of multi-armed therapeutic OV drug candidates.

These updated data generated on 37 patients treated at the highest dose levels of the Phase I demonstrated that the therapy is well tolerated and confirmed the mechanism of action of TG6002 administered IV. They were presented on September 11, 2022, in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting taking place in Paris (France) from September 9-13, 2022.

The findings are as follows:

TG6002 demonstrated good tolerability when administered weekly or on days 1,3 and 5. No major toxicities limiting the dose escalation process or the intensification of the schedule of administration were observed. Transient fever is the most common adverse event.
TG6002 is able to reach the tumor, replicate, and express its payload after IV administration.
Onset of a neutralizing antibody response is not associated with a decreased biological activity of the product.
These data further confirm the mechanism of action of the Invir.IO-based oncolytic viruses in humans.
The two IV administration schedules display different characteristics, that can both be leveraged in upcoming clinical trials. Three doses given once a week resulted in higher levels of expression of the payload than the more intensive schedule (3 injections within 5 days). The intensive schedule allowed for a longer lasting expression of the payload.
These findings support the potential of IV administration of Invir.IO-based oncolytic viruses, extending the use of these therapies to a broad range of solid tumors.

The overall Phase I program with TG6002 was aimed at establishing the tolerability and the potential different doses and administration schedules for further development. Additional data will be produced from the Phase I program and will be presented at a scientific congress in H1 2023.

Title of the poster: "Updated data of biodistribution and activity of oncolytic virus TG6002 after intravenous administration in patients with advanced gastrointestinal carcinomas"
Authors: Victor Moreno, Philippe Cassier, Bernard Doger, Emiliano Calvo, Maria De Miguel, Rocio Garcia-Carbonero, Carlos Gomez-Roca, Christiane Jungels, Sophie Sainte-Croix, Philippe Erbs, Alain Sadoun and Kaïdre Bendjama
Abstract Number: #4886
Poster Number: 392P
The abstract and the e-poster are available on the ESMO (Free ESMO Whitepaper) congress website here and the e-poster can be downloaded on the Transgene website here as well.

About the trial (NCT03724071)
This trial is a single-arm open-label Phase I/II trial evaluating the safety and tolerability of multiple ascending doses of TG6002 administered intravenously in combination with oral 5-FC, a non-cytotoxic pro-drug that can be converted in 5-FU, its active metabolite. Based on the safety profile of TG6002, several dose levels and administration schedules have been added to the initial Phase I clinical protocol. The trial has safety as primary endpoint for the Phase I. The trial also evaluates pharmacokinetic properties and biodistribution of TG6002, along with immune modulation of the tumor micro-environment. This European study enrolled patients suffering from advanced gastrointestinal carcinomas who have failed and/or are intolerant to standard therapeutic options in the Phase I part.
Dr. Philippe Cassier, M.D., Ph.D., head of the early-phase trials unit at Centre Léon Bérard (Lyon, France), is the principal investigator of the trial.

About TG6002
TG6002 has been engineered to directly kill cancer cells (oncolysis), to enable the production of a chemotherapy agent (5-FU) within the tumor, and to elicit an immune response by the body against the tumor cells. Its satisfactory safety profile after intravenous administration and its mechanism of action has been shown in human in a Phase I trial.
In preclinical experiments, TG6002 has been shown to induce the shrinkage of the primary tumor as well as the regression of distant metastases (Foloppe, et al., Molecular Therapy Oncolytics, View Source).
The production of 5-FU directly in the tumor aims to achieve a better anti-tumoral effect with limited chemotherapy-induced side effects.
TG6002 induces the production of 5-FU in the cancer cells it has infected, by enabling the local conversion of the pro-drug 5-FC (administered orally) into 5-FU. 5-FU is a common chemotherapy agent for patients with gastrointestinal cancers. This mechanism of action is based on the in-tumor expression of the proprietary FCU1 gene that has been encoded in the genome of TG6002, taking advantage of the virus selective replication in the tumor cells.
When administered systemically, 5-FU is associated with side effects that can lead to treatment discontinuation. With TG6002, 5-FU is produced within the tumor where it is expected to be present at a high concentration level in contrast to the very low levels anticipated in the rest of the patient’s body.

On September 12, 2022 Starpharma (ASX: SPL, OTCQX: SPHRY) reported that additional results from the mCRPC cohort of its Phase 2 DEP cabazitaxel trial, following completion of dosing in this cohort (Press release, Starpharma, SEP 12, 2022, View Source;mc_eid=bf52dd3418 [SID1234619441]). Treatment with DEP cabazitaxel showed a number of key advantages compared to published data for conventional cabazitaxel, including superior efficacy, as measured by longer PFS, and a lower incidence of key side effects, despite this patient cohort being relatively more heavily pre-treated.

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The new data for DEP cabazitaxel was presented in a scientific poster at the ESMO (Free ESMO Whitepaper) 2022 Congress in Paris, France, by Principal Investigator, Professor Robert Jones of the Velindre Cancer Centre in Wales. The poster is available on www.starpharma.com.

Starpharma CEO, Dr Jackie Fairley, commented:

"Starpharma is very pleased to report this additional encouraging data at the ESMO (Free ESMO Whitepaper) Congress for DEP cabazitaxel in heavily pre-treated, late-stage prostate cancer patients, including median progression-free survival for the first time, having now completed dosing in this cohort. These latest results show DEP cabazitaxel achieved both a longer duration of progression-free survival and fewer severe side effects compared to published data on Jevtana, illustrating the potential for DEP cabazitaxel to provide better outcomes for mCRPC patients.

"We are deeply appreciative of the cancer patients who have participated in this trial, along with the contribution of the clinical investigators involved in the study."

Trial and Patient Cohort Overview

Twenty-five patients with metastatic castration-resistant prostate cancer were enrolled in this cohort across five trial sites in the UK and Australia. Trial participants received an intravenous infusion of DEP cabazitaxel every 21 days, repeated for up to 12 cycles. The median time on study was 18.4 weeks.

All patients enrolled in this cohort had already been heavily pre-treated before entering the study, having previously received an average of 4 other cancer treatment types, in addition many have also had surgery and radiation. On average, patients enrolled in this study had already received more than 70 cycles/months of other treatments. Notably, 96% of patients in this trial cohort had also previously received related chemotherapies (taxanes), including docetaxel and/or conventional cabazitaxel (Jevtana). This level of pre-treatment is important to note because patients with this high level of prior cancer treatment would not be expected to respond as well to further similar therapies.

Summary of interim results

Highly encouraging anti-tumour activity for DEP cabazitaxel, including a radiological partial response (PR) for more than 45 weeks, and stable or improved secondary metastatic bone disease for up to 45 weeks;
Median progression-free survival (PFS) of 3.9 months2 for DEP cabazitaxel which is more than 30% longer than published PFS data for standard cabazitaxel (2.9 months3) (see below and Table 1) at the same dose;
100% of evaluable DEP cabazitaxel patients achieved a response in at least 1 measure of efficacy (soft tissue disease [stable disease (SD) or PR], prostate specific antigen (PSA), and/or bone disease);
90% of DEP cabazitaxel patients evaluable for a PSA response achieved a reduction in PSA, and 52% achieved a PSA reduction of 50% or more from baseline;
83% of DEP cabazitaxel patients evaluable for secondary bone disease experienced an improvement or no progression;
68% of DEP cabazitaxel patients evaluable for 2 or 3 efficacy measures achieved a response for all evaluable measures (soft tissue disease [SD or PR], PSA, and bone disease);
No DEP cabazitaxel patients required routine steroid pre-medication or daily oral steroid and only 2 patients required prophylactic G-CSF[4]; and
DEP cabazitaxel was generally well-tolerated, with TRAEs similar to those observed with standard cabazitaxel (Jevtana).
Progression-free survival

Notably, the median PFS observed in evaluable mCRPC patients treated with DEP cabazitaxel was longer than published data on Jevtana. Patients treated with DEP cabazitaxel at the recommended Phase 2 dose (20 mg/m2) achieved a composite median PFS of at least 3.9 months2. This is a more than 30% improvement in median PFS than what has been reported for patients treated with Jevtana (2.9 months3) at the same dose (20 mg/m2). Even at a higher dose of Jevtana (25 mg/m2) published data show patients treated with Jevtana achieved a median PFS of 3.5 months3 in one study and 2.8 months[5] in another, so DEP cabazitaxel (20 mg/m2) median PFS was longer.

These very encouraging findings for DEP cabazitaxel in this study were observed despite many patients being at an increased risk of neutropenic complications, due to their age (mean = 73 years) and large number of prior chemotherapy regimens. More than half the DEP cabazitaxel patients (56%2) had received at least two prior chemotherapy regimens, whereas only 16%3 of patients from published Jevtana data had received this level of prior treatment (Figure 1). DEP cabazitaxel patients received an average of 4 other cancer treatments, and more than 70 cycles/months of treatment before entry into the study.

Adverse Events

In this heavily pre-treated DEP cabazitaxel cohort, TRAEs were generally mild to moderate, and all have also been reported for Jevtana. In addition, the incidence of Grade 3 and 4 TRAEs in patients treated with DEP cabazitaxel was only 7.5%2, substantially lower than published reports for Jevtana (39.7%3) at the same dose (20 mg/m2) (see Table 2).

Notably, the incidence of Grade 3 and 4 neutropenia was 16.0%2 in this cohort of patients treated with DEP cabazitaxel, less than half of the 41.8%3 reported for patients treated with Jevtana. A lower incidence of problematic severe bone marrow toxicities was also observed in patients treated with DEP cabazitaxel compared to published data on Jevtana3. Notably, and despite the older age of this cohort, secondary prophylactic use of G-CSF was only required by 2 patients.

Patients with mCRPC in this DEP cabazitaxel study have now completed dosing. These new results, together with the previously reported interim findings (see ASX announcement dated 25 November 2021), indicate an improved and favourable efficacy and safety profile of DEP cabazitaxel compared to published data on Jevtana.

In addition to the positive Phase 2 clinical data reported here for DEP cabazitaxel in prostate cancer, encouraging efficacy signals, including multiple partial responses, have been observed in other cancer types, often in heavily pre-treated patients. These cancer types include platinum resistant ovarian cancer, and other relapsed and refractory cancers, including oesophageal squamous cell carcinoma and gastro-oesophageal junction adenocarcinoma. Starpharma is recruiting a number of additional patients with these tumour types into the trial as positive findings in these indications could expand the application of DEP cabazitaxel and its market potential. Final results from the DEP cabazitaxel trial will be reported following completion of dosing and analyses of all cohorts, however the data reported at the ESMO (Free ESMO Whitepaper) Congress will feed into ongoing licensing discussions.

DEP cabazitaxel

Developed by Starpharma, DEP cabazitaxel is a patented, dendrimer nanoparticle version of conventional cabazitaxel, which is marketed as Jevtana and widely used in the treatment of prostate cancer. Unlike standard cabazitaxel, DEP cabazitaxel is highly water soluble, does not contain toxic detergent-like excipients associated with anaphylaxis, and avoids the need for steroid pre-medication. In both preclinical and clinical studies, DEP cabazitaxel has shown an improved side effect profile, notably markedly reduced bone marrow toxicity demonstrated by lower rates of severe neutropenia, thrombocytopenia, and severe anaemia, which are all reportedly experienced by a significant proportion of patients treated with Jevtana.

On September 12, 2022 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported that preliminary results from the company’s Phase 1 clinical trial evaluating zanidatamab zovodotin (ZW49) for the treatment of HER2-positive tumors (Press release, Zymeworks, SEP 12, 2022, View Source [SID1234619440]). The presentation, entitled "Preliminary Results From a Phase 1 Study Using the Bispecific, Human Epidermal Growth Factor 2 (HER2)-targeting Antibody-drug Conjugate (ADC) zanidatamab zovodotin (ZW49) in Solid Cancers", was presented by Komal Jhaveri, MD, FACP, medical oncologist, Memorial Sloan Kettering Cancer Center in NYC, in a mini-oral presentation today during the European Society for Medical Oncology Annual Congress at the Paris Expo Porte de Versailles in Paris, France.

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A total of 77 patients were enrolled in this first-in-human trial, which was designed to determine the maximum tolerated dose of zanidatamab zovodotin, characterize its safety and tolerability, and evaluate anti-tumor activity in HER2-expressing cancers as monotherapy. The patients represented a variety of HER2-expressing cancers including breast, gastroesophageal, ovarian, endometrial, bladder, biliary tract, anal, colorectal, pancreatic and lung. At the time of the analysis, the maximum tolerated dose had not yet been reached.

Commenting on the data, Dr. Jhaveri noted, "The preliminary results of this trial are very encouraging. Zanidatamab zovodotin dosed on an every three week (Q3W) schedule is active and has a manageable safety profile. I am excited to see further clinical development of zanidatmab zovodotin across a variety of HER2-expressing cancers."

In the trial, zanidatamab zovodotin was shown to have a manageable safety profile with the majority of adverse events being Grade 1 or 2 in severity. In patients with HER2-positive cancers treated with zanidatamab zovodotin at 2.5 mg/kg Q3W (dose escalation + dose expansion), the confirmed objective response rate was 31% and the disease control rate was 72%. The Phase 1 clinical trial is ongoing and continues to enroll patients to study safety, tolerability and activity for an alternate qW dosing regimen. The Company expects to present results of this dosing regimen at a medical meeting in 2023.

"We are grateful to the patients who participated in this trial and appreciate the collaborative efforts and dedication of the outstanding group of clinical investigators who are participating in this Phase 1 study," said Neil Josephson, MD, Chief Medical Officer of Zymeworks. "These promising results provide significant momentum for the further clinical development of zanidatamab zovodotin, as a monotherapy, and in combination with standard of care agents, for the treatment of cancers expressing HER2 or harboring HER2 gene alterations."

Conference Call

Dr. Jhaveri’s complete presentation at the ESMO (Free ESMO Whitepaper) 2022 Congress is available for review on Zymeworks’ website. Zymeworks will hold a conference call to discuss Dr. Jhaveri’s presentation and future clinical development plans for zanidatamab zovodotin on Monday, September 12th at 4:30 pm EST. Interested parties can access the live webcast via Zymeworks’ website at View Source A recorded replay will be accessible after the event through the Zymeworks website.

Disclosure: Dr. Jhaveri has a consulting relationship with Zymeworks.

On September 12, 2022 Volastra Therapeutics, an oncology company focused on exploiting chromosomal instability to treat cancer, reported it has been named as one of Fierce Biotech’s 2022 "Fierce 15," designating it as one of the most promising early-stage biotechnology companies in the industry (Press release, Volastra Therapeutics, SEP 12, 2022, View Source;utm_medium=rss&utm_campaign=volastra-therapeutics-named-one-of-fierce-biotechs-fierce-15-companies-of-2022 [SID1234619438]).

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"It is an honor and tremendous validation of our team and progress to be among the Fierce 15," said Charles Hugh-Jones, M.D., FRCP, Chief Executive Officer at Volastra. "Our unique understanding of chromosomal instability combined with our proprietary CINtech platform allows us to develop potentially life-saving therapies for patients. I am extremely proud of what we have accomplished in just the last three years, and the promise of what lies ahead."

Michael Su, Ph.D., the company’s Chief Scientific Officer, added, "We are particularly excited about our lead program, a KIF18A inhibitor that is on track to begin a Phase 1 trial in the second half of 2023. We recently announced compelling preclinical data supporting the potential of Volastra’s KIF18A inhibitor to induce tumor regression."

Now in its 20th Fierce 15 selection, Fierce Biotech evaluates hundreds of early-stage companies from around the world for its annual list, which celebrates the spirit of being "fierce"— championing innovation and creativity in the face of strong competition. Winners are selected based on a variety of factors, such as the strength of their scientific approach, leadership, technology, partnerships, venture backers, and scale of unmet needs they are solving for.

On September 12, 2022 Upsher-Smith Laboratories, LLC (Upsher-Smith) reported that it has expanded its ongoing partnership with Appco Pharma LLC (Appco) with the addition of a near-term generic product opportunity to its portfolio (Press release, Upsher-Smith Laboratories, SEP 12, 2022, View Source [SID1234619437]). This collaboration is part of Upsher-Smith’s company-wide effort to grow the Company’s portfolio of products through strategic partnerships and product acquisitions.

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"This agreement further expands an already solid working relationship between Upsher-Smith and Appco," said Rich Fisher, President and COO, Upsher-Smith. "Appco has extensive skills and experience in the development of diverse dosage forms that span a wide range of therapeutic areas. Our long-standing partnership has yielded a number of commercial-stage products. We are pleased to add their development strengths to our core competencies and expand Upsher-Smith’s product portfolio to accelerate growth in the U.S."

"We are pleased to add one more product to our partnership with Upsher-Smith," said Srini Paruchuri, COO, Appco. "Appco highly values Upsher-Smith’s strength in sales and marketing which complements Appco’s development and manufacturing capabilities. We look forward to expanding and growing this partnership.’’

Upsher-Smith will open its world-class manufacturing facility in Maple Grove, MN later this year. The new, 270,000 square foot facility will have fully up-to-date serialization and packaging capabilities and has capacity and capabilities that can support contract manufacturing for third parties. To learn more, visit www.upsher-smith.com.