On June 28, 2021 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapeutics targeting fundamental biological pathways of cancers, reported key clinical and regulatory updates across its pipeline (Press release, Zentalis Pharmaceuticals, JUN 28, 2021, View Source [SID1234584411]).

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!

"We continue to build substantial value in Zentalis’ portfolio, driving toward approval of our differentiated cancer therapeutics to help patients worldwide," commented Dr. Anthony Sun, Chairman and Chief Executive Officer of Zentalis. "Based on our clinical results reported to date, the emerging clinical profiles of our candidates support the potential for best-in-class positioning for a range of tumor types addressing large patient populations, is use as a monotherapy or in combinations. In particular, we are excited about the compelling profile of ZN-c3, our WEE1 inhibitor, as it demonstrated additional, deepening and durable tumor responses as a monotherapy in heavily pretreated solid tumors. These promising data set the stage for the many upcoming planned trials – two of which have the potential to be registrational monotherapy studies in indications with significant unmet medical needs. We look forward to a productive second half of 2021, as we focus on delivering on our milestones across our entire pipeline."

ZN-c3: Oral WEE1 Inhibitor for Solid Tumors

Updates from our ongoing trials of ZN-c3 continue to support the potential for our WEE1 inhibitor, ZN-c3, to be both first-in-class and best-in-class. Since our last update at AACR (Free AACR Whitepaper) in April 2021, and as of the data cut-off date of May 15, 2021:

The 2 unconfirmed Partial Responses (PRs) reported at AACR (Free AACR Whitepaper) were confirmed, bringing the total number of confirmed PRs from our monotherapy trial from 3 to 5. Since AACR (Free AACR Whitepaper), an additional unconfirmed PR was reported in a patient with uterine serous carcinoma (USC), resulting in 3 out of 7 USC patients enrolled having responded to treatment. Overall, the objective response rate (ORR) in the USC population increased from 40% to 43% based on RECIST criteria.
Additionally, within the exceptional responder population in the Phase 1 monotherapy trial, we have observed a patient with an ongoing treatment duration of more than 8 months, with a deepening response of 65% to 69% tumor size decrease based on RECIST criteria.
Lower overall severe hematological adverse event rates – severe neutropenia adverse event rates decreased from 2.9% to 2.2% with an additional 11 patients enrolled since AACR (Free AACR Whitepaper) 2021.
Following an End-of-Phase 1 meeting, the U.S. Food and Drug Administration (FDA) concurred in principle with the proposal that ZN-c3 has the potential for an accelerated approval pathway based on the proposed global study design of a Phase 2 monotherapy trial in women with recurrent or persistent USC. The trial has initiated with multiple sites open.
Zentalis is planning to launch a biomarker-driven Phase 2 study pending FDA feedback. The tumor-agnostic trial will investigate ZN-c3 in patients with solid tumors that express the identified predictive biomarker, and is expected to initiate by year-end.
ZN-c3 has received orphan drug designation, and rare pediatric disease designation from the FDA for pediatric osteosarcoma. The Phase 1/2 trial of ZN-c3 in combination with chemotherapy in pediatric patients with osteosarcoma is expected to initiate in 3Q 2021. If ZN-c3 were to obtain approval for the designated indication, it could be eligible for a rare pediatric disease priority voucher upon approval.
Zentalis will also support two planned additional investigator-initiated trials: a trial with the Ivy Brain Center in glioblastoma multiforme (GBM) and a trial with immunotherapy with Dana Farber in triple negative breast cancer.
Zentalis’ China JV Zentera is advancing corresponding clinical trials in China with ZN-c3.
ZN-c5: Oral SERD for ER+/HER2- Advanced or Metastatic Breast Cancer

Based on the interim results from multiple ongoing trials, ZN-c5 has demonstrated the potential to support best-in-class tolerability in both monotherapy and combination settings, with strong clinical results observed. As of May 11, 2021, the following data were collected:

Monotherapy Trials (Expansion and Dose Escalation)

In total, 56 patients with 2 median prior lines of treatment were evaluated for safety and efficacy. Across all doses from 50 mg QD to 300 mg QD, the observed CBR was 33% and the ORR was 5%. ZN-c5 generated 2 PRs at the 150 mg and 300 mg doses. Adverse events (AEs) were found in less than 10% of the patients and there were no observed cases of bradycardia, visual disturbances, QTC or dizziness. Of note, treatment related diarrhea adverse event rate was 3.6%, with only grade 1 or 2 events observed. The Phase 2 monotherapy trial has been initiated and Zentalis may take multiple doses into this study.

An oral dose of 50 mg QD (n=16) demonstrated a CBR of 40%, with many patients in this dose cohort remaining on study drug and in the trial. Final determination of the monotherapy RP2D will occur following completion of this 50 mg QD dose cohort.
Combination Dose Escalation Trials with Pfizer’s CDK4/6 Palbociclib and Lilly’s CDK4 and 6 Abemaciclib

Tolerability data for ZN-c5 suggests it could be best-in-class in oral SERDS, making this candidate ideal for further evaluation in combination. The two separate trials will continue to enroll patients and the Company expects to report interim results in 1H 2022 from one or more of these trials.
Window of Opportunity Trial

The Window of Opportunity trial (n=35) demonstrated ER degradation across all doses tested.
ZN-d5: Highly Selective Oral BCL-2 Inhibitor for Hematologic Tumors

The Phase 1 monotherapy dose-escalation trial, initiated in 4Q 2020, has enrolled 14 patients with relapsed/refractory non-Hodgkin’s lymphoma (NHL) thus far in the fifth dose cohort. Additionally, no dose-limiting toxicities have been identified. Patients with acute myeloid leukemia will begin enrollment in 3Q 2021. Interim results from this Phase 1 trial are expected in 1H 2022.
ZN-e4: 3rd Generation Oral EGFR Inhibitor for Non-Small-Cell Lung Carcinoma

The Phase 1/2 dose-escalation trial in patients with advanced non-small cell lung cancer is ongoing with 26 patients (both osimertinib-naïve and experienced) enrolled to date. ZN-e4 has been well-tolerated at all doses as of the March 25, 2021 data cut-off, and clinical activity was identified at doses greater than 80 mg QD. Interim results from the Phase 1/2 trial are expected in 4Q 2021.
Webcast Event:
Zentalis will host a webcast event today, June 28, 2021 at 8:30 a.m. EDT. To register and access the event, the webcast link is available on the Investors & Media section of the Zentalis website at www.zentalis.com.

On June 28, 2021 BioVaxys Technology Corp. (CSE: BIOV, FRA:5LB,OTCQB:BVAXF) ("BioVaxys" or the "Company") reported that non-brokered private placement (the "Private Placement") consisting of up to 9,090,909 units ("Units") at a price of $0.22 per Unit for total gross proceeds of up to approximately $2,000,000 (Press release, BioVaxys Technology, JUN 28, 2021, View Source [SID1234584428]). Each Unit consists of one common share (a "Common Share") and one whole Common Share purchase warrant (a "Warrant"). Each Warrant is exercisable for one additional Common Share at an exercise price of $0.50 for a period of 30 months.

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!

All securities issued pursuant to the Private Placement are subject to a statutory hold period of four months and one day from the date of issuance. The Company may pay cash finder’s fees on all or a portion of the Private Placement.

The Company intends to use the net proceeds of the Private Placement to advance its research and development programs and for working capital. Closing of the Private Placement is subject customary conditions of closing, including the approval of the Canadian Securities Exchange, and is expected to complete within the next week.

On June 28, 2021 Prescient Therapeutics (ASX:PTX) reported that it is developing a next-generation CAR-T platform called OmniCAR, based on technology licensed from the University of Pennsylvania, a pioneer in the space, as well as Oxford University (Press release, Prescient Therapeutics, JUN 28, 2021, View Source;utm_medium=rss&utm_campaign=tragedy-struck-the-car-t-space-this-month-with-a-us-company-halting-a-trial-of-its-lead-therapy-after-the-deaths-of-two-patients-a-sobering-reminder-of-the-dangers-involved-in-cell-therapy-image-ge [SID1234584529]).

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!

Chief executive Steven Yatomi-Clarke acknowledges that some industry observers had assumed that safety was no longer a serious issue for CAR-T, but this latest tragedy puts safety back into sharp focus. Prescient’s OmniCAR platform seeks to make CAR-T therapy safer by enabling clinicians to control its activity even once infused into a patients

Right now, CAR-T involves injecting living cells into a patient’s body – their own genetically modified blood.

"Once these current generation CAR-T cells are infused, they propagate of their own accord, and you’ve got no way of controlling it," Yatomi-Clarke says.

"If a doctor gives you any other medication, if you have a bad reaction, what do they tell you to do? To stop taking it, reduce the dose, or maybe change medications. But when the medicine is a living cell you can’t yet do that."

‘Druggable and controllable’
But OmniCAR is different from current generation CAR-Ts. It is designed to be controlled even after it is infused into the patients. The key to this is the modular nature of the platform, which separates the CAR-T cell and the part that binds to the cancer cells. The therapy is viable but inactive until the two components come together and bind the cancer cells.

"We’re making CAR-T cells druggable and controllable," Yatomi-Clarke says. "Basically we are combing all of the good things about a T-cell – it can kill a cancer cell like nothing else – but giving it the control and flexibility that a doctor typically expects from a traditional medicine."

Yatomi-Clarke says traditional CAR-T therapies are like sending soldiers into battle with a single weapon, a single map, and no communication and control in the field.

"Whereas what we’ve got is a soldier, because of this modularity, we can arm it with any weapon, send it anywhere, direct it against any target, and have full communication and control."

The activity of the OmniCAR cells can be increased or decreased to achieve safe and efficacious levels. And even if the patient has a deleterious effect, a physician could simply stop administering the binder, and the engineered white blood cells would switch off.

"Because you can control it, it’s not a runaway train," Yatomi-Clarke says.

The doctor could later try the therapy again at a lower dose, without the need to manufacture and administer new CAR-T cells, he said.

This plug-and-play approach is also useful if the cancer mutates, which is a problem facing current generation CAR-T. Currently in that case the patient would be left with "all of the bad side effects of CAR-T, and zero benefits, Yatomi-Clarke says. But with OmniCAR the physician could simply switch out the binder, and the T-cells would be redirected to the new target.

As Stockhead reported on Thursday, Prescient confirmed that manufacturing is complete for a range of binders that target multiple cancers.

The eventual goal is to have off-the-shelf cell therapies, so doctors don’t have to spend 22 days harvesting and manufacturing a patient’s cells so they can be infused into their body, Yatomi-Clarke says.

On June 28, 2021 Philogen reported that Co-founder, CEO and CSO, Prof. Dario Neri has been invited to participate at the 19th Annual Global Healthcare Conference organised by Morgan Stanley on September 9-15, 2021 (Press release, Philogen, JUN 28, 2021, View Source [SID1234584927])

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 format includes virtual fireside chats for (C-level only) and one-on-one meetings, providing management the opportunity to meet with shareholders and top institutional investors throughout the day.

On June 28, 2021 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to SNDX-5613 for the treatment of adult and pediatric patients with relapsed or refractory acute leukemias harboring a mixed lineage leukemia rearranged (MLLr) or nucleophosmin (NPM1) mutation. SNDX-5613 is the Company’s highly selective, oral menin inhibitor (Press release, Syndax, JUN 28, 2021, View Source [SID1234584396]).

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!

"Genetically-defined acute leukemias represent an underserved area marked by particularly poor prognosis and limited therapeutic options," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "As we move toward initiating our pivotal study, receipt of FTD from the FDA underscores SNDX-5613’s potential to meaningfully improve outcomes for patients with MLLr and NPM1 mutant acute leukemias."

About Fast Track Designation

Fast Track Designation is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fulfill an unmet medical need, enabling drugs to reach patients earlier. The FDA created this process to help deliver important new drugs to patients earlier and it covers a broad range of serious illnesses. These clinical programs may also be eligible to apply for Accelerated Approval and Priority Review if relevant criteria are met.

About SNDX-5613

SNDX-5613 is a potent, selective, small molecule inhibitor of the menin-MLL binding interaction that is being developed for the treatment of mixed lineage leukemia rearranged (MLLr) acute leukemias including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), and NPM1 mutant AML. In preclinical models of MLLr acute leukemias, SNDX-5613 demonstrated robust, dose-dependent inhibition of tumor growth, resulting in a marked survival benefit. Menin-MLL interaction inhibitors have also demonstrated robust treatment benefit in multiple preclinical models of NPM1 mutant AML, which represents the most frequent genetic abnormality in adult AML. SNDX-5613 is currently being evaluated in the Company’s AUGMENT-101 Phase 1/2 open-label clinical trial for the treatment of relapsed/refractory (R/R) acute leukemias. SNDX-5613 was granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with AML, and Fast Track designation for the treatment of adult and pediatric patients with relapsed or refractory acute leukemias harboring a mixed lineage leukemia rearranged MLLr or NPM1 mutation.

About Mixed Lineage Leukemia Rearranged Acute Leukemias

Rearrangements of the MLL gene give rise to mixed lineage leukemia rearranged (MLLr) acute leukemias known to have a poor prognosis, with less than 25% of adult patients surviving past five years. MLL rearrangements produce fusion proteins that require interaction with the protein called menin to drive leukemic cancer growth. Disruption of the menin-MLLr interaction has been shown to halt the growth of MLLr leukemic cells. MLLr leukemias, which are routinely diagnosed through currently available cytogenetic or molecular diagnostic techniques, occur in approximately 80% of infant acute leukemias and up to 10% of all acute leukemias. There are currently no approved therapies indicated for MLLr leukemias.

About NPM1 Mutant Acute Myeloid Leukemia

NPM1 mutant acute myeloid leukemia (AML), which is distinguished by point mutations in the NPM1 gene that drive the leukemic phenotype, is the most common type of cytogenetically normal adult AML and represents approximately 30% of all adult AML cases. This subtype of AML has a five year overall survival rate of approximately 50%. Similar to mixed lineage leukemia rearranged (MLLr) leukemias, NPM1 mutant AML is highly dependent on the expression of specific developmental genes shown to be negatively impacted by inhibitors of the menin-MLL interaction. NPM1 mutant AML is routinely diagnosed through currently available screening techniques. There are currently no approved therapies indicated for NPM1 mutant AML.