On October 13, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, and EQRx, a new type of pharmaceutical company committed to developing and delivering important new medicines to patients at radically lower prices, reported a clinical collaboration to evaluate elzovantinib (TPX-0022), Turning Point’s drug candidate targeting MET, SRC, and CSF1R, in combination with aumolertinib, EQRx’s drug candidate targeting EGFR, in patients with EGFR mutant MET-amplified advanced non-small cell lung cancer (NSCLC) (Press release, Turning Point Therapeutics, OCT 13, 2021, View Source [SID1234591242]).

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!

Under the terms of the agreement, Turning Point will sponsor and conduct a Phase 1b/2 clinical trial to evaluate the safety, tolerability and preliminary efficacy of the combination regimen and will assume all costs associated with the trial. EQRx will provide aumolertinib at no cost. Turning Point is targeting initiation of the clinical trial in 2022, pending filing of an investigational new drug (IND) application by the U.S. Food and Drug Administration (FDA).

Preclinical data suggest the combination of MET and EGFR inhibition has the potential to increase anti-tumor activity based on complementary mechanisms. It is estimated that 15 to 20% of patients who progress on a first-line EGFR inhibitor develop MET amplification as the basis of acquired resistance.

"We believe the combination of elzovantinib with aumolertinib could provide an important potential treatment option for patients who develop MET amplification as acquired resistance to an EGFR inhibitor, where no approved therapies are available today," said Athena Countouriotis, M.D., president and chief executive officer of Turning Point. "We are pleased to have EQRx as our collaboration partner and look forward to initiating our Phase 1b/2 SHIELD-2 study of the combination."

"This collaboration marks the launch of the EQRx-Inside Platform, a unique development-to-commercialization platform designed to accelerate access to potentially life-enhancing combination therapies and create efficiencies for partners, physicians, and health systems," said Melanie Nallicheri, chief executive officer of EQRx. "We are pleased to partner with Turning Point and believe this collaboration will be the first of many that will broaden patient access to important combination clinical trials and innovative potential cancer therapies such as aumolertinib and elzovantinib."

About Elzovantinib
Elzovantinib is a multi-targeted orally bioavailable Type I TKI with a novel macrocyclic structure that potently inhibits MET, SRC and CSF1R, in preclinical assays. MET alterations, including point mutations, amplifications, fusions, exon 14 skipping, and the generation of HGF-MET autocrine loops have been reported in many cancers. SRC inhibition may have the potential to reduce or abolish certain oncogenic signaling, and the targeting of CSF1R leads to the modulation of tumor associated macrophages.

Preliminary clinical data from the ongoing Phase 1 SHIELD-1 study of single-agent elzovantinib presented at the 2021 AACR (Free AACR Whitepaper)-NCI-EORTC Conference in October 2021, demonstrated preliminary clinical activity, including objective responses across multiple tumor types and a generally tolerable safety profile. The U.S. Food and Drug Administration has granted elzovantinib Orphan Drug designation for the treatment of gastric cancer, including gastroesophageal junction cancer, and Fast Track designation for the treatment of patients with MET-amplified advanced or metastatic gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma after prior chemotherapy.

About Aumolertinib
Aumolertinib 110 mg once-daily is a prescription medicine approved in China as AMEILE for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by a genomic test, who have progressed on or after prior EGFR TKI therapy. Aumolertinib is a novel, irreversible EGFR-TKI that selectively inhibits both EGFR sensitizing and resistance mutations with high selectivity over wild-type EGFR. Aumolertinib was approved in China in March 2020 based on the large single arm Phase 2 APOLLO study in second-line settings. The ongoing Phase 3 AENEAS trial in first-line settings met its primary endpoint of progression-free survival and topline results were presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.

Hansoh Pharma and EQRx have partnered to expand global access to aumolertinib. EQRx holds the development and commercialization rights to aumolertinib outside of Greater China and is pursuing regulatory discussions in multiple countries.

On October 13, 2021 Prescient Therapeutics Limited (ASX:PTX) reported that it is presenting new preclinical data on OmniCAR at the Cell & Gene Meeting on the Mesa in Carlsbad, California (Press release, Prescient Therapeutics, OCT 13, 2021, View Source;utm_medium=rss&utm_campaign=prescient-presents-new-data-on-key-omnicar-features-for-car-t-cell-therapy-at-cell-gene-meeting [SID1234591219]). Bringing together some prominent decision makers on therapies including cell therapy, the Cell & Gene Meeting on the Mesa is considered as one of the foremost conferences in the sector.

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 data highlights the exceptional capabilities of OmniCAR to deliver next generation cell therapies that are controllable, flexible, & adaptable in nature. They can target multiple cancer antigens.

The findings are significant not only in the development of Prescient’s in-house OmniCAR programs, but in the development of the overall platform and demonstrating novel features relevant to potential partners and collaborators.

CAR-T therapy & the challenges in its efficacy
CAR-T is a cell therapy effectively working against certain blood cancers by genetically altering a patient’s own T-cells by adding a new receptor (CAR) to recognise cancer antigens. However, the field of CAR-T therapy is encountering some challenges related to time, cost, safety and targets.

CAR-T Therapy against cancer

Source: PTX Update (13 October 2021)

For CAR-T to succeed in Acute Myeloid Leukemia (AML) and overcome challenges that limit their broader use, it needs to consider that AML patients are not in a state to undergo vigorous therapies such as CAR-T. AML has the potential to mutate mid-therapy, making single CARTs non-effective. In case multiple current gen CAR-T therapies were available, resistant patients are expected to advance before subsequent therapies are manufactured for them. OmniCAR is uniquely placed to address these challenges for CAR-T in AML.

Current generation CAR-T therapy is also facing similar issues in treating GBM (an aggressive brain cancer, glioblastoma multiforme). The composition of GBM and its ability to rapidly mutate limits the effectiveness of CAR-Ts only targeting a single antigen which may result in relapse. Conversely, CAR-Ts targeting multiple antigens have demonstrated anti-tumor responses and more importantly prevented antigen escape in vivo.

ALSO READ: Prescient Therapeutics’ (ASX:PTX) AML trial progresses to next dosing level

Steven Yatomi-Clarke and Dr Rebecca Lim will be presenting an ‘OmniCAR Explainer’ session next Tuesday at 11am (AEDT) where they will explain the OmniCAR platform and latest results in more detail. Please click here to register for the session.

OmniCAR addressing the problems raised in CAR-T therapy
Prescient Therapeutics’ OmniCAR platform

Source: PTX Update (13 October 2021)

OmniCAR is a modularised universal immune receptor (UIR) platform enabling controllable T-cell activity and multi-antigen targeting with a single cell product. The platform uses technology exclusively from CAR-T pioneer the University of Pennsylvania (UPenn), as well as Oxford University. It has the potential to enhance the safety and efficacy of any CAR-T therapy, enabling in-house development of next-generation CAR-T therapies, and by dramatically improving external CAR-T programs. It will create opportunities for collaboration and business development in the CAR-T field.

Prescient’s New Data Demonstrating Key OmniCAR Features for CAR-T cell Therapy

Dose-response: In cell therapies such as CAR-T therapy, where living cells that continue to grow and divide are administered to patients, efficacy is less predictable and controllable. OmniCAR aims to combine the potent cytotoxicity of cell therapy with the control and predictability of a conventional drug.
Re-arming: Single infusions of CAR-T cells may be insufficient to drive meaningful patient outcomes in many cancers, especially solid tumours. OmniCAR-T cells pre-armed with Her2 binders demonstrated potent ability to kill cancer cells expressing Her2.
Sequential arming & re-direction: OmniCAR-T cells pre-armed with EGFRviii binders demonstrated rapid cytotoxicity against those GBM cells expressing EGFRviii. Also, OmniCAR cells can be redirected to a different antigen target upon administration of a different SpyTagged binder without needing new cells. In each case, OmniCAR exhibited highly target tumour killing.

Source: PTX Update (13 October 2021)

ALSO READ: Prescient Therapeutics (ASX:PTX) aims to cash in on OmniCAR Programs

Here’s a remark by Prescient’s Director of Scientific Affairs, Dr Rebecca Lim:

"Critical features of OmniCAR have been tested in recent months and the data continue to be extremely positive. Our most recent work conducted in collaboration with the Peter MacCallum Cancer Centre showed that OmniCAR-T cells begin antigen-directed killing of tumour cells in vitro as soon as they are armed. The team also showed that OmniCAR-T cells could be re-armed and continue to kill tumour cells without loss of cytotoxicity."

She added, "Excitingly, we saw for the first time the real-time ‘switchability’ of the OmniCAR system where the tumour killing ability of the OmniCAR-T cells could be redirected towards a different antigen through the addition of a different binder. These early wins are extremely encouraging, and we look forward to the next phase of pre-clinical testing where the OmniCAR technology will be put through its paces using gold standard cancer models."

Stock information: PTX share price surged by 6.818% and closed the day’s trade at AU$0.235 on the Australian Securities Exchange (ASX), with a market capital of AU$151.44 million.

On October 13, 2021 Synaffix B.V., a biotechnology company focused on commercializing its clinical-stage platform technology for the development of antibody-drug conjugates (ADCs) with best-in-class therapeutic index reported that it will present new data regarding its topoisomerase 1 inhibitor linker-payload based on exatecan (SYNtecan E), at the World ADC Conference on 13 October 2021 (Press release, Synaffix, OCT 13, 2021, View Source [SID1234591211]):

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!

Title: GlycoConnect ADCs Based on Topoisomerase 1 Inhibitor Exatecan (SYNtecan E) Show Excellent In Vivo Efficacy and Tolerability
Time: 9:30pm CEST / 3:30pm EDT / 12:30 PDT
Authors: Floris van Delft, Remon van Geel, Jorin Hoogenboom, Marloes Wijdeven, Laureen de Bever, Sorraya Popal, Jord van Schaik, Sander van Berkel
Synaffix utilizes GlycoConnect, a proprietary technology based on the native glycan of monoclonal antibodies, which is used as a privileged conjugation site for ADCs. In addition, a highly polar spacer technology (HydraSpace) enables the conjugation of any cytotoxic, hydrophobic payload, providing ADCs with significantly expanded therapeutic index (TI).

Camptothecins form a class of clinically relevant chemotherapy drugs based on their ability to inhibit DNA topoisomerase 1 while also demonstrating excellent potential as payloads for antibody-drug conjugates (ADCs), as exemplified by the recent market approvals of Enhertu and Trodelvy.

Synaffix’s data demonstrate that:

Exatecan, a clinically validated and potent campothecin, is readily combined with Synaffix’s HydraSpace technology, resulting in the SYNtecan E linker-payload
GlycoConnect ADCs of trastuzumab were generated by conjugation of SYNtecan E to antibodies and evaluated for efficacy and tolerability
Complete tumor regression was observed in a mouse xenograft study (BT-474) after a single dose, while safety studies in mice corroborated high tolerability of SYNtecan E ADCs
Prof. Floris van Delft, CSO of Synaffix, said: "We are delighted to be presenting new data on our groundbreaking technologies at this distinguished annual meeting. As the ADC community once again comes together to share its latest research, Synaffix is excited to showcase its continued efforts to develop truly best-in-class ADC therapeutics."

In the last few months, Synaffix has signed significant ADC technology out-licensing agreements with Kyowa Kirin, a global specialty pharmaceutical company; ProfoundBio, an emerging oncology biotherapeutics company; and Innovent Biologics, a leading biopharmaceutical company developing innovative medicines for the treatment of major diseases. These come in addition to earlier collaborations with ADC Therapeutics, Mersana Therapeutics and Shanghai Miracogen. Three ADCs using Synaffix’s technology are in the clinic.

On October 13, 2021 Prescient Therapeutics (PTX) reported that it will present new results for its OmniCAR drug at the Cell & Gene Meeting on Mesa in California (Press release, Prescient Therapeutics, OCT 13, 2021, https://themarketherald.com.au/prescient-therapeutics-asxptx-to-present-new-omnicar-data-at-conference-2021-10-13/?utm_source=rss&utm_medium=rss&utm_campaign=prescient-therapeutics-asxptx-to-present-new-omnicar-data-at-conference [SID1234591210]).

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 conference brings together senior executives and decision makers on therapies including cell therapy.

OmniCAR is a universal immune receptor platform allowing controllable T-cell activity and multi-antigen targeting with a single cell product.

The most recent work with the Peter MacCallum Cancer Centre showed that OmniCAR-T cells begin antigen-directed killing of tumour cells in vitro as soon as they are armed.

It was also discovered that OmniCAR-T cells could be re-armed and continue to kill tumour cells without loss of cytotoxicity.

These new results show the important capabilities of OmniCAR to deliver next generation cell therapies that are controllable and able to target multiple cancer antigens.

Prescient’s Director of Scientific Affairs Rebecca Lim is pleased with the new results.

"Excitingly, we saw for the first time the real-time ‘switchability’ of the OmniCAR system where the tumour killing ability of the OmniCAR-T cells could be redirected towards a different antigen through the addition of a different binder," Dr Lim said.

"These early wins are extremely encouraging, and we look forward to the next phase
of pre-clinical testing where the OmniCAR technology will be put through its paces using gold standard cancer models."

Dose response
A dose response relationship is the correlation between the amount of drug given the magnitude of response. Normally, higher doses lead to greater effects.

In cell therapies such as CAR-T therapy, where living cells that continue to grow and divide are administrated to patients, effects are considerably less predictable and controllable.

The aim of OmniCAR is to combine the potent cytotoxicity of cell therapy with the control and predictability of a conventional drug.

Prescient treated glioblastoma multiforme (GBM) cells with OmniCAR-T cells armed with varying amounts of SpyTagged EGFRviii and Her2 binders to test whether different doses of binders resulted in equal levels of CAR-T activity.

In both cases, OmniCAR showed dose-dependent tumour killing activity, with the ability to control OmniCAR-T cell activity.

Re-arming
Single infusions of CAR-T cells may be insufficient to drive meaningful patient outcomes in many cancers, especially solid tumours.

Prescient has now shown this "re-arming" capability of OmniCAR. OmniCAR-T cells pre-armed with Her2 binders demonstrated potent ability to kill cancer cells extracting Her2. Following this, the cells were washed and rested for several days, resulting in unarmed OmniCAR cells.

These same OmniCAR-T cells were then capable of being re-armed with Her2 binders, and once again showed the same results.

"This demonstrates that OmniCAR cells can be unarmed, re-armed and still kill with near identical fidelity. It is another example of the flexible yet predictable activity of OmniCAR cells," the company said.

Managing Director and CEO Steven Yatomi-Clarke is looking forward to present this data at the Cell & Gene Meeting this week.

"It is very pleasing to see a large body of work accomplished successfully so quickly and is a credit to the Prescient team and the incredible collaborators at Peter MacCallum Cancer Centre," he said.

"Importantly, none of these tests have even been optimised, so we have yet to see the true limits of this technology. OmniCAR is proving to be a predictable and powerful system to work with. We look forward to sharing updates as our programs progress."

On the market this morning, Prescient was up 9.09 per cent and is trading at 24 cents per share at 11:40 am AEDT.

On October 13, 2021 Compass, Inc. (NYSE: COMP), a leading real estate technology company, reported that its third quarter 2021 financial results will be released after market close on Wednesday, November 10, 2021 (Press release, Compass Therapeutics, OCT 13, 2021, View Source [SID1234591199]). The company will host a conference call and webcast to discuss its results that afternoon at 4:30 p.m. ET / 1:30 p.m. PT.

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!

Call details are as follows:

The conference call will be accessible via the Internet on the Compass Investor Relations website, View Source

Please register in advance to access the live conference call at: Compass Inc. 3Q21 Earnings Conference Call.

An audio recording of the conference call will be available for replay shortly after the call’s completion for up to 90 days following the call. To access the replay, visit the Events and Presentations section of the Compass Investor Relations website.