On September 26, 2022 Tollys, a biopharmaceutical company developing TL-532, the first anti-cancer immunotherapy based on a new generation of synthetic toll-like receptor 3 (TLR3) specific agonist, reported that it will present the latest data on TL-532 at the Oligonucleotide Therapeutics Society (OTS) congress in Phoenix (Arizona, United States), on October 3rd 2022 (Poster number 30) (Press release, Tollys, SEP 26, 2022, View Source [SID1234621405]).

The new data shows the anti-tumor activity of TL-532, a 70 base pair double stranded RNA oligonucleotide. It features a well-defined homogenous structure demonstrating strict TLR3 specificity and resulting in optimal tolerance. As such, TL-532 has the potential to be the best-in-class and first-to-market TLR3 agonist.

"We’re very proud to present these new results for TL-532. The new data on our compound’s tolerance shown in non-human primates is especially encouraging," said Marc Bonnin, PhD, head of the discovery unit at Tollys, who will present the data at the OTS congress. "This proof of tolerance, combined with the strict TLR3 specificity, and its well described mechanism of action brings us one step closer to our goal to be first-to-market."

In the coming months, Tollys plans to accelerate the development of its TLR3 agonist candidate for systemic administration in immuno-oncology.

Key highlights from the poster
Title: ‘TL-532, a novel rationally designed Toll-like receptor 3 agonist, induces tumor-specific apoptosis, immune stimulation, life-long anti-tumor auto-vaccination, and reverses resistance to immune checkpoint inhibitors’

Authors: THIERRY Sylvain, OURFALI Saïd, BOUCARD-JOURDIN Mathilde, MAADADI Sarah, PERRET Clémence, RENOUX Chloé, BERTON Aurore, VEY Nelly, BALLET Caroline, COLOMBEL Marc, WERLE Bettina, BONNIN Marc

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TL-532 is a druggable double stranded RNA, chemically synthetized and perfectly defined demonstrating strict TLR3 specificity, composed of blocks of poly(A:U) (Polyadenylic–polyuridylic acid) and polyI-C (Polyinosinic:polycytidylic acid)
After intravenous-bolus injections in non-human primates, TL-532 demonstrated optimal tolerance with Maximum Tolerated Dose ≥ 280mg/kg
In monotherapy:
TL-532 led to promising anti-cancer activity (Tumor Growth Inhibition (TGI) of 88%, Tumor Growth Delay (TGD) of 370%) resulting in a Complete Response (CR) rate of 35% and, interestingly, in life-long tumor auto-vaccination after consecutive rechallenges up to 30 months
Ex vivo and in vivo the tumor cell death by apoptosis induced by TL-532 was associated with a tumor microenvironment switch and activation of conventional Dendritic Cells (cDCs) and Cytotoxic T-Lymphocytes (CTLs) at the tumor site
In combo-therapy:
TL-532, when combined with anti-PD-L1, demonstrated a remarkable ability to overcome Immune Checkpoint Inhibitors (ICI) tumor-resistance, leading to doubling of the CR rate
About TL-532
TL-532 is a chemically synthetized double stranded RNA with a well-defined homogenous structure demonstrating strict TLR3 specificity, resulting in optimal tolerance. As such, TL-532 has the potential to be the best-in-class and first-to-market TLR3 agonist. TL-532 was shown to have a triple mechanism of action inducing 1) death by apoptosis selective to cancer cells – not in normal cells -, leading to the in-situ release of tumor specific antigens, 2) activation of the myeloid dendritic cells of the immune system to mount a specific T-cell response against the tumor antigens and 3) a switch of the tumor microenvironment by producing cytokines and chemokines which are unfavorable to tumor development. The result is the immunogenic cell death of tumor cells, accompanied by an auto-vaccination preventing the recurrence of cancer.

On September 26, 2022 Vivoryon Therapeutics N.V. (Euronext Amsterdam: VVY; NL00150002Q7) (Vivoryon), a clinical stage company focused on the discovery and development of small molecule medicines to modulate the activity and stability of pathologically altered proteins, reported that it will publish its financial results for the first six months of 2022 and provide a corporate update on September 30, 2022 (Press release, Vivoryon Therapeutics, SEP 26, 2022, View Source [SID1234621402]). The Company will host a conference call and webcast open to the public. The report will be available for download on the Company’s website (View Source).

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On September 26, 2022 Kupando, a pioneering biopharmaceutical company developing TLR 4/7 agonists that stimulate innate immunity for use in oncology and infectious diseases, reported the closing of its Series A funding round which raised €13 million (Press release, Kupando, SEP 26, 2022, View Source [SID1234621401]).

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The funds will be used to complete IND-enabling work and to initiate the clinical development of Kupando’s lead candidate KUP101 in a solid tumor indication. KUP101 is the only TLR 4/7 agonist in development, and consists of two small molecules, a TLR 4 agonist and a TLR 7 agonist, co-encapsulated in a liposomal formulation. The compounds induce a broad immune response, which will facilitate their development as an anti-tumor agent, as a stand-alone product, in combination with other anti-tumor modalities, or a prophylactic vaccine for infectious diseases. The induction of cross-reactive antibodies and a broad cellular response are promising features for a broad portfolio of indications, in particular where different strains and antigens play a role like influenza, HPV and others. A high target specificity in the absence of relevant off-targets are indicators for a promising safety profile.

The investment was led by Remiges Ventures and co-led by Life Care Partners with an additional investment by Brandenburg Kapital, High-Tech Gründerfonds, Ventura Biomed Investors and undisclosed family offices.

Kazuhiko Nonomura, PhD Principal at Remiges Ventures, the lead investor said: "We are impressed by the tremendous progress made by Kupando since its inception. Kupando is a real pioneer in the development of a novel innate immunity stimulator, and we look forward to working with the team and supporting the advancement of KUP101 into clinical development."

Pierre Morgon, PharmD, LL.M, MBA, Chairman at Kupando commented: "We are welcoming all our new investors of this round. We thank them for their trust in this truly disruptive approach which has the potential to provide new therapeutic and prophylactic options in the fields of oncology and infectious diseases. We believe that the highly experienced management team will enable the company to progress through this next stage of development."

Johanna Holldack, CEO at Kupando added: "Having new investors choosing to fund us is a great validation of our company strategy and pioneering approach, and we look forward to advancing our lead candidate towards clinical development thanks to their support. It is really exciting to now have the opportunity to develop compounds that can make a difference in the treatment of solid tumors and prevention of infectious diseases in terms of efficacy, safety and affordability.

The Kupando Board comprises of Pierre Morgon, PharmD, LL.M, MBA, as Chairman and Wolfram Nothaft, MD, as Deputy Chairman, and of three Board members: Kazuhiko Nonomura, PhD (representing Remiges Ventures), Gerhard Ries, PhD (representing LifeCare Partners) and Thomas Krause (representing Brandenburg Kapital).

On September 26, 2022 CellOrigin Biotech (Hangzhou) Co., Ltd. reported it has made a global strategic collaboration agreement with Qilu Pharma to develop, manufacture and commercialize proprietary "off-the-shelf" induced pluripotent stem cell- (iPSC) derived Chimeric Antigen Receptor Macrophages (CAR-iMAC) for cancer immunotherapy (Press release, CellOrigin Biotech, SEP 26, 2022, View Source [SID1234621400]).

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The collaboration will take advantages of technologies and expertise from both parties, as well as integrate capabilities of R&D, manufacturing and marketing to develop CAR-iMAC clinical products aiming for solid tumors.

"Innovation and offering the best products that benefit patients are the core values that CellOrigin Biotech and Qilu Pharma both appreciate," said Dr. Jin Zhang, the Co-Founder of CellOrigin Biotech and a Principal Investigator of Zhejiang University, one of the top universities in China. "This is what brings us together."

"We are very excited to collaborate with Qilu Pharma because of its prestige in the field of Chinese pharmaceutical industry, as well as its tremendous track records on drug development," said Dr. Jiansong Tong, the Chief Executive Officer at CellOrigin Biotech. "Meanwhile, we will continue to seek other potential collaborators to jointly develop our innovative anti-tumor CAR-iMac cell products."

"CellOrigin Biotech is a startup company established by a group of outstanding scientists who have tremendous experiences both in R&D research and cGMP manufacture. It focused on developing innovative technologies in cell therapy and building valuable pipeline of products. It is an ideal strategic partner for novel cell therapy, and it is our pleasure to collaborate with such a great biotech company," said Qilu Pharma.

On September 23, 2022 Lacerta Therapeutics, a leader in the development of adeno-associated virus (AAV) technologies for the treatment of central nervous system (CNS) diseases, reported a new AAV capsid licensing and research collaboration agreement with Prevail Therapeutics, a wholly owned subsidiary of Eli Lilly and Company (Press release, Lacerta Therapeutics, SEP 23, 2022, View Source [SID1234622161]). The collaboration will focus on the discovery and development of novel AAV capsids for CNS diseases.

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"We are eager to initiate this exciting collaborative work with our new partners at Prevail. The goal is to broaden the AAV medicines cabinet by improving the safety, potency, and manufacturability of novel AAV capsid variants for CNS indications," said Edgardo Rodriguez-Lebron, Chief Executive Officer of Lacerta Therapeutics. "With this agreement, Lacerta gains its third clinical and commercial partner as we continue to push towards our shared goal of improving the life of patients with intractable neurodegenerative diseases."

As a part of the collaboration, Prevail will receive rights to utilize one of Lacerta’s novel AAV capsids for select undisclosed CNS targets. In addition, Lacerta’s proprietary AAV capsid platform will be utilized to discover and develop novel AAV capsids that are optimized to target desired CNS tissues and cell types. The collaboration will leverage Lacerta’s established expertise in AAV technologies and Prevail’s development and clinical capabilities, with the goal of accelerating development of gene therapies for patients with neurodegenerative disorders.

"We are excited to be collaborating with Lacerta on the discovery of novel AAV capsids with improved CNS delivery to advance the development of new medicines by Prevail and the Lilly Institute for Genetic Medicine," said Mansuo Shannon, Chief Scientific Officer of Prevail Therapeutics. "We believe this will allow us to move promising therapeutics more quickly to the clinic to study novel genetic medicines for diseases with high unmet need."

Lacerta will lead capsid discovery, screening, and validation, while Prevail will complete preclinical and Investigational New Drug-enabling studies with therapeutic payloads. Prevail will be responsible for all manufacturing, clinical development, and commercialization. Under the terms of the agreement, Lacerta will receive an upfront payment and will be eligible for development and commercial milestones, as well as tiered royalties on future net sales of products that incorporate capsids covered under the collaboration. Lilly will also provide Lacerta with new financing under the terms of a convertible promissory note agreement.