On June 23, 2020 Achilles Therapeutics ("Achilles"), a clinical stage biopharmaceutical company developing personalised cancer immunotherapies, reported that it has dosed the first patient in a Phase I/II CHIRON study of a clonal neoantigen T cell (cNeT) therapy in patients with advanced non-small cell lung cancer (NSCLC) (Press release, Achilles Therapeutics, JUN 23, 2020, View Source [SID1234561374]). In May 2020, Achilles dosed the first patient with cNeT in its Phase I/II THETIS study in recurrent or metastatic malignant melanoma.

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Achilles’ precision tumour-infiltrating lymphocyte (TIL) therapy uses cutting edge genomics to selectively target patient specific clonal neoantigens – targets which are believed to be present on all tumour cells – this approach has the potential to transform the treatment of cancer.

The CHIRON study is an open-label, multi-centre Phase I/II trial evaluating the safety, tolerability and clinical activity of cNeT therapy as a single dose in adult patients with advanced metastatic NSCLC. The trial is expected to recruit approximately 40 patients and report interim data in the first half of 2021. Recruitment is ongoing across sites in the UK, with additional sites to open in the US and Europe. Link to Study.

"The cNeT dosing of the first patient with NSCLC marks another important milestone for Achilles. Our opportunity to serve patients is tremendous as NSCLC remains one of the most prevalent and poorly served of the solid tumours," said Dr Iraj Ali, CEO of Achilles Therapeutics. "As with our melanoma study, the CHIRON study is an entirely personalised cell therapy designed to be exquisitely specific and effective and has the potential to help us fundamentally change how certain cancers are treated."

"We have been working closely with the Achilles team to design and set up this study across the UK, and are delighted to be dosing the first NSCLC patient with this innovative experimental cell therapy here at University College London Hospital (UCLH), the lead clinical site," said Dr Martin Forster, Associate Professor in Medical Oncology and Study Chief Investigator.

Achilles is developing personalised T cell therapies for solid tumours targeting clonal neoantigens: protein markers unique to each patient that are present on the surface of all cancer cells. Using its PELEUS bioinformatics platform, Achilles can identify clonal neoantigens from each patient’s unique tumour profile which are present on every cancer cell. Achilles uses its proprietary process to manufacture T cells (cNeT) which exquisitely target a specific set of clonal neoantigens in each patient. Targeting multiple clonal neoantigens that are present on all cancer cells, but not on healthy cells, reduces the risk that new mutations can induce immune evasion and therapeutic resistance, and allows individualised treatments to target and destroy tumours without harming healthy tissue.

On June 23, 2020 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that the United States Patent and Trademark Office (USPTO) has issued U.S. Patent No. US 10,689,454 which covers compositions of matter directed to Alligator’s drug candidate ATOR-1017, its wholly owned 4-1BB antibody in clinical Phase I development for the treatment of metastasized cancer (Press release, Alligator Bioscience, JUN 23, 2020, View Source [SID1234561373]). This is the first granted US patent related to ATOR-1017 and its earliest expiry year is 2037.

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"ATOR-1017 is one of our lead clinical assets and I am pleased to get this formal confirmation of our long-term exclusive rights. The patent approval illustrates our active IP strategy, maximizing protection for Alligator’s entire project portfolio in all key global markets, including the US," commented Per Norlén, CEO at Alligator Bioscience.

ATOR-1017 activates 4-1BB receptors which increases the ability of the immune system to detect and kill tumor cells. ATOR-1017 has a unique profile related to the fact that its immune-stimulatory function is stronger in areas where immune cells are abundant, notably in tumors. This creates an opportunity for a strong immune activation that can increase efficacy and reduce side effects for the patient.

The ongoing Phase I study is a dose escalation study in patients with advanced cancer. The study is conducted at three different clinics in Sweden and is planned to include up to 50 patients. Recruitment was temporarily paused in March and April 2020 due to the covid-19 pandemic but has been resumed. The primary objective of the study is to assess the safety and tolerability of ATOR-1017 and to determine the recommended dose for the subsequent Phase II studies.

The information was submitted for publication, through the agency of the contact person set out above, at 08:30 a.m. CEST on June 23, 2020.

On June 22, 2020 Ankrin Therapeutics has been awarded 2.4 million DKK from Innovation Fund Denmark’s ‘Innobooster’ program (Press release, Ankrin Therapeutics, JUN 22, 2020, View Source [SID1234572466]). The Grant will support Ankrin’s discovery programs targeting so-called homologous recombination (HR), a critical DNA damage response (DDR) mechanism in cancer cells. Ankrin’s novel concept provides a new approach to inhibit HR with potential to treat a broad spectrum of cancers.

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On June 22, 2020 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported preclinical studies highlighting the potential for its lead drug candidate, repotrectinib, to increase the effectiveness of KRAS-G12C and MEK inhibitors in cancer models, and for its next-generation ALK inhibitor candidate, TPX-0131, to overcome ALK-resistant mutations (Press release, Turning Point Therapeutics, JUN 22, 2020, View Source [SID1234564369]).

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The studies were included as part of three poster presentations at today’s virtual annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

"Feedback reactivation and bypass signaling may limit the efficacy of KRAS-G12C and MEK inhibitors against KRAS-driven tumors, and our encouraging preclinical data shows how repotrectinib has the potential to increase the anti-tumor effects by inhibiting SRC, FAK and JAK2 signaling," said Athena Countouriotis, M.D., president and chief executive officer. "We look forward to building upon these preclinical combination studies as we explore the potential for repotrectinib to address a broad set of oncogenic-driven solid tumors.

"In addition, we are excited to share for the first time preclinical data for our fourth drug candidate, TPX-0131, a next generation ALK inhibitor in IND enabling studies. We are encouraged by TPX-0131’s preclinical potency against both wildtype ALK and the most common resistant mutations."

Jessica Lin, M.D., Attending Physician in the Center for Thoracic Cancers at Massachusetts General Hospital Cancer Center and Henri and Belinda Termeer Center for Targeted Therapies, and Instructor in Medicine at Harvard Medical School said: "Resistant mutations following treatment with approved ALK inhibitors remain a challenge for patients, especially the difficult to treat G1202R/del solvent front mutation which can occur in up to 42 percent of patients who develop a resistance mutation, and compound mutations that develop after the recently approved agent Lorbrena. The preclinical potency of TPX-0131 against these mutations suggests that it warrants further study."

Repotrectinib Combination Studies
The preclinical antitumor activities of repotrectinib in combination with proxy molecules for AMG510, an investigational KRAS-G12C inhibitor, and trametinib, an approved MEK inhibitor were highlighted for the first time in two poster presentations. The studies show repotrectinib’s inhibition of SRC, FAK and JAK2 at therapeutically relevant concentrations, which in combination with AMG510 or trametinib demonstrated a synergistic effect over the single agent by reducing tumor cell growth and enhancing tumor cell death. The repotrectinib-trametinib combination studies were replicated across panels of KRAS mutant non-small cell lung, colorectal and pancreatic cancer cell lines that harbor a spectrum of KRAS mutations.

The frequently mutated Kirsten Rat Sarcoma (KRAS) viral oncogene is associated with a broad range of human cancers, including approximately 25 percent of non-small cell lung, 45 percent of colorectal and 75 percent of pancreatic cancers. Therapeutic targeting of KRAS has proven challenging, in part due to resistance and adaptive upregulation of alternative signaling pathways that promote tumor cell survival, as well as concurrent secretion of various cytokines and growth factors.

In preclinical models, repotrectinib inhibits SRC and FAK signaling, a key pathway for oncogenic resistance, and JAK2, a driver of cytokine secretion pathways.

TPX-0131, a Next-Generation ALK Inhibitor
TPX-0131 has been internally designed with a compact macrocyclic structure to bind completely within the ATP binding site of ALK. In preclinical studies, TPX-0131 potently inhibits wildtype ALK and numerous ALK mutations, in particular the clinically observed G1202R solvent-front mutation and G1202R/L1196M compound mutation.

In cell proliferation assays presented at AACR (Free AACR Whitepaper), TPX-0131 exhibited greater potency against wildtype ALK as compared to proxy molecules for approved front-line ALK inhibitors crizotinib, alectinib, brigatinib and ceritinib, and comparable potency to a proxy molecule for approved ALK inhibitor, lorlatinib. TPX-0131 demonstrated more than 100-fold greater potency against the G1202R solvent-front mutation as compared to proxy molecules for the approved ALK inhibitors. Additionally, TPX-0131 is the most potent inhibitor against a range of EML4-ALK compound mutations while prior generation ALK inhibitors tested have shown moderate to no activity.

Anaplastic lymphoma kinase- (ALK) driven tumors are estimated to represent up to 7 percent of driver oncogenes in non-small cell lung cancer and in one study of patients who develop a resistance mutation, G1202R was reported in approximately 42 percent of patients, and compound mutations have been reported in approximately 35 percent of patients who developed resistance following treatment with lorlatinib.

The three posters presented today are:

Title: Repotrectinib increases effectiveness of KRAS-G12C inhibitors in KRAS-G12C mutant cancer models via simultaneous SRC/FAK/JAK2 inhibition
Abstract Number: 1958

Title: Repotrectinib increases effectiveness of MEK inhibitor trametinib in KRAS mutant cancer models via simultaneous SRC/FAK/JAK2 inhibition
Abstract Number: 1957

Title: TPX-0131: A next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitorsbstract Number: 5226

On June 22, 2020 Targovax ASA, a clinical stage immuno-oncology company developing oncolytic viruses to target hard-to-treat solid tumors, reported that Magnus Jäderberg, Chief Medical Officer of Targovax, will present an overview of the company at the upcoming Virtual European Biotech Investor Day 2020 hosted by Solebury Trout, Goodwin, Deutsche Bank and Nasdaq (Press release, Targovax, JUN 22, 2020, View Source [SID1234564003]).

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Participants will be able to submit questions electronically during the presentation, with answers provided at the discretion of the company on an individual basis afterwards.

Details are as follows:
Date/Time: Thursday June 25, at 5:30 pm CET / 11:30 am EDT
To access the presentation, please login here.
Archive of the event will be available on the Company’s website at www.targovax.com.