On March 12, 2020 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of the Company’s proprietary targeted biologic therapeutics, engineered toxin bodies (ETBs), reported financial results for the fourth quarter of 2019 (Press release, Molecular Templates, MAR 12, 2020, View Source [SID1234555493]). As of December 31, 2019, MTEM’s cash and investments totaled $126.6 million, which is expected to fund operations into 2022.

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"In 2019, we made important progress by advancing our pipeline programs, establishing a new collaboration outside of oncology with a premier partner, and strengthening our balance sheet with a successful equity financing," said Eric Poma, Ph.D., Molecular Templates’ Chief Executive and Scientific Officer. "We now have five ongoing studies across three clinical programs: three Phase 2 studies for MT-3724, a Phase 1 study for MT-5111, and a Phase 1 study with our partner Takeda for TAK-169. We also expect our earlier stage programs to advance in 2020, including an IND filing for MT-6402 (our PD-L1 ETB with antigen seeding), preclinical data presentations on ETBs against new targets, and continued progress in our multi-target collaborations with Takeda and Vertex."

Company Highlights and Upcoming Milestones

Corporate

On November 18, 2019, MTEM and Vertex Pharmaceuticals announced a strategic research collaboration to discover and develop novel targeted conditioning regimens that may enhance the hematopoietic stem cell transplant process, including transplants conducted as part of treatment with ex vivo CRISPR/Cas9 gene editing therapies such as CTX001. Under the collaboration, MTEM will conduct research activities for the use of ETBs for up to two targets selected by Vertex. The initial research will be focused on discovering a novel conditioning regimen using MTEM’s ETB technology platform. In addition, Vertex has an option to select a second target as part of the collaboration. Vertex made an up-front payment of $38 million to MTEM, including an equity investment. MTEM is also eligible to receive future development, regulatory and sales milestones and option payments of up to $522 million (across two targets) and tiered royalty payments on future sales.
On November 21, 2019, MTEM announced the pricing of an underwritten equity offering, the net proceeds of which were approximately $53.4 million, after deducting underwriting discounts and commissions and other estimated offering expenses payable by MTEM.
On February 19, 2020, MTEM announced the initiation of dosing in a Phase 1 study investigating TAK-169 in patients with relapsed/refractory multiple myeloma. Co-developed with Takeda Pharmaceutical Company Limited ("Takeda"), TAK-169 is a potential first-in-class CD38-targeting ETB. As a result of achieving this milestone, MTEM received a $10 million payment from Takeda.
MT-3724 (CD20 ETB)

At the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2019, MTEM presented the final results from the MT-3724 Phase 1/1b monotherapy study. The presentation included safety data on doses from 5-100 μg/kg, and efficacy data on 13 serum rituximab negative (RTX-neg) diffuse large B-cell lymphoma (DLBCL) or mixed DLBCL/FL subjects of whom 5 responded (38% objective response rate) across the range of 5 to 50 μg/kg doses. Of the 5 responses, 2 were complete responses (CRs) and 3 were partial responses (PRs). Three patients had stable disease (including 2 patients with 49% and 47% tumor reductions) and 5 patients had progressive disease. Of the 5 serum RTX-neg subjects with DLBCL who received MT-3724 at 50 μg/kg, the maximum tolerated dose (MTD), 3 responded (2 CRs, 1 PR).
MTEM is currently conducting three ongoing Phase 2 studies in relapsed/refractory DLBCL: a monotherapy study that has the potential to be pivotal, a combination study with chemotherapy, and a combination study with lenalidomide.
In January 2020, MTEM reported that the combination study with lenalidomide has demonstrated preliminary evidence of tolerability and efficacy with lenalidomide at standard doses and MT-3724 at 10 μg/kg. MT-3724 dosing at higher doses with lenalidomide is ongoing.
In January 2020, MTEM reported that the combination study with GemOx has demonstrated preliminary evidence of efficacy but Grade 2 innate immune adverse effects were seen with standard doses of gemcitabine and oxaliplatin and 10 μg/kg doses of MT-3724. The study protocol has been amended to include a revised schedule in which MT-3724 dosing is initially sequenced with GemOx dosing.
MTEM expects to report updates on all three MT-3724 studies throughout 2020.
TAK-169 (CD38 ETB)

Takeda and MTEM are currently conducting a Phase 1 study for TAK-169 in relapsed/refractory multiple myeloma.
In December 2019, TAK-169 received Orphan Drug Designation from the FDA.
MT-5111 (HER2 ETB)

In December 2019, MTEM presented preclinical data on MT-5111 at the San Antonio Breast Cancer Symposium (SABCS).
The Phase 1 study of MT-5111 in HER2-positive cancers is ongoing with multiple sites open for enrollment.
MTEM expects to announce interim clinical results from the MT-5111 Phase 1 study in 2Q20 and additional data from the dose escalation portion of the study in 4Q20.
Research

MTEM expects to file an IND application for MT-6402, its ETB targeting PD-L1 (with antigen seeding), in 2H20.
Several other ETB candidates are in preclinical development against targets including CTLA-4, SLAMF-7, and CD45.
In 2020, MTEM expects to present preclinical data on new targets and new ETBs at conferences.
Financial Results

The net loss attributable to common shareholders for the fourth quarter of 2019 was $15.9 million, or $0.41 per basic and diluted share. This compares with a net loss attributable to common shareholders of $6.6 million, or $0.18 per basic and diluted share, for the same period in 2018.

Revenues for the fourth quarter of 2019 were $6.2 million, compared to $4.7 million for the same period in 2018. Revenues for the fourth quarter of 2019 were comprised of revenues from collaborative research and development agreements with Takeda, and grant revenue from CPRIT. Total research and development expenses for the fourth quarter of 2019 were $16.6 million, compared with $7.6 million for the same period in 2018. Total general and administrative expenses for the fourth quarter of 2019 were $6.0 million, compared with $3.9 million for the same period in 2018.

On March 12, 2020 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a biotechnology company focused on developing cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported the latest in its series of Q&A articles that are conducted with some of the key management members of PharmaCyte’s research and development team related to its upcoming clinical trial in locally advanced, inoperable pancreatic cancer (LAPC) (Press release, PharmaCyte Biotech, MAR 12, 2020, View Source [SID1234555509]).

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This interview-style Q&A article with Dr. Gerald W. Crabtree, PharmaCyte’s Chief Operating Officer, aims to address the company’s recent FDA-required tests and the submission process of its Investigational New Drug application (IND) to the U.S. Food and Drug Administration (FDA). Dr. Crabtree has spent almost 50 years working in academia and biotech and pharmaceutical companies, with the majority of that experience being in the development of drugs and treatments for cancer. He has supervised and coordinated the development of multiple drug candidates, prepared clinical protocols, investigator brochures, monographs and research and review articles.

A highlight of Dr. Crabtree’s professional career was his tenure as Director of Project Planning and Management (Oncology and Immunology) at Bristol-Myers Squibb (BMS) from 1990 to 1997. While at BMS, Dr. Crabtree established and directed a department that monitored and coordinated the development of all oncologic and immunologic drugs from initial discovery through regulatory approval within BMS and served as Project Manager for the development of the major anticancer agent, Taxol, the leading product candidate under development at BMS at that time. Taxol ultimately became a multi-billion-dollar drug for BMS and is still widely used in combination with other drugs to treat a variety of cancers.

Currently PharmaCyte is awaiting the testing results from its pyrogenicity test, an FDA-required test, that has been discussed in the past but that wasn’t part of the release testing. Can you tell us what this test is and why this test is important?

Dr. Crabtree: "In short, the U.S. FDA wants to know if the Cell-in-a-Box capsules that we use in our treatment for LAPC have any fever-inducing properties, and a pyrogenicity test is how we provide this necessary data to the FDA.

"The pyrogenicity test is important to the FDA because, to my knowledge, no other treatment for a particular tumor combines both a cancer prodrug and a biologic where that biologic consists of live, genetically engineered human cells that have been encapsulated using a unique cellulose-based technology. Because of this, the FDA wants to know whether the capsules made using the cellulose-based Cell-in-a-Box technology have any fever-inducing properties.

"In order for PharmaCyte to conduct this test, hundreds of empty Cell-in-a-Box capsules had to be produced by our partner Austrianova at its manufacturing facility in Thailand. During this time consuming and expensive process, Austrianova filled a number of syringes (identical to the syringes it used for our clinical trial product) with the empty Cell-in-a-Box capsules and then froze those syringes using the same freezing medium that we used for our clinical trial product as though the capsules were full of live cells. Following the production of the empty capsules, the resultant material was shipped to the U.S. where the pyrogenicity test is being conducted.

"To conduct the test, a protocol had to be developed, and PharmaCyte had to wait its turn in the queue to get underway. The actual test, which uses three rabbits that are injected with a matrix made up of crushed Cell-in-a-Box capsules and saline, only takes a few days to complete; however, the overall timeline to prepare for and complete the tests, and then prepare an audited report of the results that will be submitted to the FDA as part of PharmaCyte’s IND package, takes over a month in total after the frozen empty capsules arrived at the laboratory in the U.S."

Given your experience in bringing drugs to market through FDA clinical trials, can you explain what goes into an IND submission?

Dr. Crabtree: "The complexity and size of an IND most often depends upon the stage of development of a particular product. For example, if an IND is filed requesting permission to conduct an initial Phase 1 clinical trial and the product in question is a new drug, the IND contains information on how the drug was made, preclinical and animal testing data that may give some initial information on the type of tumor to attack and perhaps some idea of the dose range of the new drug that might be effective, as well as some idea of the type and severity of side effects caused by the drug. That’s pretty much it.

"Meanwhile, those requirements are in stark contrast to the IND that we will be submitting to the FDA. We are seeking FDA approval to conduct a ‘late-phase’ Phase 2 clinical trial that combines a well-known, established cancer prodrug (ifosfamide) and a biologic component that consists of genetically engineered human cells that have been encapsulated using a very unique cellulose-based, cell encapsulation technology (Cell-in-a-Box). Much of the IND that we will submit will be concerned with the latter. For example, how were the genetically engineered human cells made, where in the genome of those cells was the genetic alteration placed, etc.

"Also, we must completely address the Cell-in-a Box technology. How was the technology developed? Each step of the technology’s development must be explained in detail and with verified and validated reports. What is the history of this technology? Signed and verified reports of everything must be included in PharmaCyte’s IND package.

"Then, we must fully document the manufacturing of the final product. Each and every change made along the way to the final successful manufacturing ‘runs’ of the product must be documented in detail. All of the tests on the final product must also be fully documented.

"But, even with all of this information, the IND is not finished yet because we still have to supply the FDA with major medical documents, such as (i) the clinical trial protocol, (ii) the Investigator’s Brochure, (iii) the Informed Consent Form that each patient will review with their oncologist and sign before he or she can participate in the trial, (iv) the Angiography Guidelines to instruct interventional radiologists on how to place the Cell-in-a-Box capsules with the live human cells inside them as close to the pancreas tumor as possible; (v) a Pharmacy manual and (vi) at least three months of stability study data to show the frozen clinical trial product will work as it was designed to work months after it was manufactured."

Who is assisting PharmaCyte in the IND submission process and has the process to prepare the IND already begun?

Dr. Crabtree: "From the above, I hope our shareholders can better understand that our IND submission will be broad in scope and massive in size and that PharmaCyte could not do this alone. We are most grateful for the efforts put into assembling the IND by our consultants at Austrianova, Facet Life Sciences, cGMP Validation, Medpace, Practical Clinical and Dr. Manual Hidalgo and Dr. Matthias Löhr.

"Preparations for the IND began quite some time ago and are still on-going. We are going as fast as responsibly possible. Facet Life Sciences, our regulatory affairs consultant, will be submitting the completed IND application to the FDA on PharmaCyte’s behalf."

Does PharmaCyte pay a fee to submit the IND?

Dr. Crabtree: "The FDA does not require a fee for the filing of an IND. This has been verified by Facet Life Sciences, our regulatory affairs consultant."

To learn more about PharmaCyte’s pancreatic cancer treatment and how it works inside the body to treat locally advanced inoperable pancreatic cancer, we encourage you to watch the company’s documentary video complete with medical animations at: View Source

On March 12, 2020 Helix BioPharma Corp. (TSX: "HBP") ("Helix" or the "Company"), an immuno-oncology company developing innovative drug candidates for the prevention and treatment of cancer, reported it has closed a private placement financing of 5,042,016 units of the Company ("Units") at a price of $1.0332 per Unit, and the concurrent disposition of 1,708,023 shares of the Company’s Polish subsidiary, Helix Immuno-Oncology S.A. ("HIO"), to a third-party purchaser, representing an 15.5% equity stake in HIO (together with the Units, the "Purchased Securities"), for aggregate gross proceeds of CAD $6,000,000, or $1.19 per Purchased Security (Press release, Helix BioPharma, MAR 12, 2020, View Source [SID1234555544]).

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Each Unit is comprised of one common share and one common share purchase warrant. Each common share purchase warrant will entitle the holder to purchase one common share at an exercise price of $1.67 and have an expiry of five years from the date of issuance. The terms of the private placement also included the concurrent disposition by the Company of 1,708,023 shares of HIO, representing 15.5% of the outstanding shares of HIO. Following the disposition, the Company owns 51% of the outstanding shares of HIO.

The Company intends to use the net proceeds of the private placement for working capital and research and development activities.

ACM Alpha Consulting Management AG provided financial advisory services to Helix in connection with the private placement.

On March 12, 2020 Kymera Therapeutics Inc., a biotechnology company pioneering targeted protein degradation to invent breakthrough protein degrader medicines for patients, reported the closing of a $102 million Series C financing (Press release, Kymera Therapeutics, MAR 12, 2020, View Source [SID1234555448]). The round was led by Biotechnology Value Fund (BVF) and Redmile Group with participation from Wellington Management Company, Bain Capital Life Sciences, funds managed by Janus Henderson Investors and BlackRock, Rock Springs Capital and a large US-based, healthcare-focused fund. Existing investors also participated in the round.

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Kymera also received a strategic investment from The Leukemia & Lymphoma Society‘s Therapy Acceleration Program (LLS TAP) directed toward advancing the company’s work to treat blood-based cancers.

"We are very excited to be joined by a top-tier group of investors as we continue on our path to become a fully integrated biotech company," said Nello Mainolfi, PhD, co-founder, President and CEO of Kymera Therapeutics. "We are well capitalized to advance up to three programs to the clinic by next year, while we continue to enhance our best-in-class platform to unlock new biology and invent new medicines."

Kymera’s Pegasus targeted protein degradation platform harnesses the body’s natural protein recycling machinery to degrade disease-causing proteins, with a focus on un-drugged nodes in validated pathways currently inaccessible with conventional therapeutics.

Kymera‘s lead program targets IRAK4, a protein known to play a significant role in inflammation mediated by toll-like and IL-1 receptors. Kymera is planning to advance its IRAK4 degrader program in a variety of autoinflammatory and autoimmune diseases, as well as in precision-medicine targeted oncology indications. The company is also developing novel protein degrader therapies to target STAT3, an un-drugged oncogenic transcription factor as well as a driver of inflammation and fibrosis, in a range of cancers and chronic diseases.

"Targeted protein degradation is one of the most promising new therapeutic modalities, with the potential to transform medicine as we know it. Kymera is leading the way with an incredible team, a sophisticated drug discovery platform and important new protein degrader therapies designed to address the most elusive drug targets" said Bruce Booth, DPhil, co-founder, Chairman of the Board of Kymera Therapeutics and partner at Atlas Venture.

On March 12, 2020 CymaBay Therapeutics, Inc. (NASDAQ: CBAY), a clinical-stage biopharmaceutical company focused on developing therapies for liver and other chronic diseases with high unmet need, reported corporate updates and financial results for the fourth quarter and fiscal year ended December 31, 2019 (Press release, CymaBay Therapeutics, MAR 12, 2020, View Source [SID1234555479]).

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"Since announcing the decision to halt the development of seladelpar last November, we have been focused on two parallel initiatives: an investigation of the unexpected histologic findings identified by study pathologists in the Phase 2b study of seladelpar in NASH, and an evaluation of strategic alternatives to maximize shareholder value," said Sujal Shah, President and CEO of CymaBay. "Our investigation includes several key activities that will be essential for us to understand the nature and significance of the findings and have the requisite follow-up dialogue with the FDA which we are planning for before the end of the second quarter."

Shah continued, "In parallel to this investigation, our executive team and board have been focused on a comprehensive evaluation of strategic alternatives and cost-cutting initiatives. While we remain committed to completing the investigation, we believe these efforts are prudent in order to make decisions expeditiously once we gain needed clarity on the potential path forward for seladelpar."

Recent Business Highlights

The development of seladelpar was halted in all indications after consulting with expert liver pathologists and hepatologists and in consideration of patient safety. The FDA agreed with this decision, formally placed the seladelpar program on clinical hold for all indications, and subsequently provided input on plans to further investigate the situation. Since then, CymaBay has commenced an in-depth review of the Phase 2b NASH findings. This investigation includes three activities intended to confirm and subsequently understand the significance of the findings identified by study pathologists:
First, a comprehensive collection and review of data including patient demographics, medical history, concomitant medications and a broad set of biochemical markers.
Second, a blinded, independent review of baseline and end of treatment biopsies by several, world-renowned liver pathologists. The independent pathology review will include an accepted pathology scoring framework, known as the Ishak Modified HAI scoring system, to quantitatively characterize features of histology present in our patient population both at baseline and at end-of-treatment. Among these features includes a scoring for the presence and severity of interface hepatitis which is not quantified in the existing framework for scoring NASH pathology.
Third, a formal pathology and clinical hepatology review panel meeting that CymaBay anticipates convening in the middle of the second quarter during which experts will review all information gathered to provide a consensus and independent determination of the role of seladelpar in the Phase 2b NASH findings. This panel will allow for a properly informed dialogue with FDA regarding seladelpar development.

Completed reading of the Phase 2b NASH end-of-treatment biopsies by study pathologists. Preliminary results reported below are for the 152 patients out of the 181 patients enrolled in the study with paired biopsies at entry and end-of-study:
Phase 2b Preliminary Topline Results

Resolution of NASH defined as patients having a NAFLD Activity Score (NAS) of 0 or 1 for lobular inflammation and 0 for hepatocellular ballooning.
Patients that did not have end-of-study biopsies are not included in reported histology endpoints.
Measured changes from baseline to end-of-treatment in liver enzymes including ALT, AST, GGT and ALP, resembled the pattern of meaningful reductions previously reported at week 12.
Implemented cost containment and restructuring program following the decision to place the seladelpar program on hold in order to minimize expenses and conserve capital. As part of this program, CymaBay froze hiring, significantly scaled-back future procurement plans, reduced its work force by more than 60% and scaled down or cancelled many existing contracts for goods and services. The size of the Board of Directors has also been decreased from nine to five seats.

As a result of these actions, CymaBay recorded a $5.1 million restructuring charge during the fourth quarter which includes $2.9 million of employee severance costs, $0.9 million of non-cash stock-based compensation expense associated with the acceleration of stock options of certain terminated employees, and $1.3 million of charges associated with the termination of certain contract manufacturing agreements.

Held $190.9 million in cash, cash equivalents and short-term investments at December 31, 2019.
Fourth Quarter and Year Ended December 31, 2019 Financial Results

Research and development expenses for the three and twelve months ended December 31, 2019 were $20.9 million and $83.8 million, respectively. This compared to R&D expenses of $16.4 million and $58.1 million for the three and twelve months ended December 31, 2018, respectively. Prior to the decision to halt development of seladelpar in November 2019, research and development expenses in the fourth quarter and twelve months ended 2019 were generally higher than in the corresponding periods in 2018 due to expanding clinical trial activities related to the PBC Phase 3 clinical trial, PSC Phase 2 clinical trial, and other NDA-enabling studies.

General and administrative expenses for the three and twelve months ended December 31, 2019 were $4.5 million and $19.2 million, respectively. This compared to $4.2 million and $14.4 million for the three and twelve months ended December 31, 2018, respectively. Prior to the decision to halt development of seladelpar, G&A expenses in the fourth quarter and twelve months ended 2019 were higher than in the corresponding periods in 2018 as a result of higher labor costs and other administrative expenses necessary to support expanding development activities.

Net loss for the three and twelve months ended December 31, 2019 was $29.4 million, or ($0.43) per diluted share, and $102.8 million, or ($1.53) per diluted share, respectively. This compared to net loss of $19.4 million, or ($0.32) per diluted share, and $72.5 million, or ($1.26) per diluted share, in the three and twelve months ended December 31, 2018, respectively. Net loss was higher largely due to increases in operating expenses, including restructuring charges.
Conference Call Details

CymaBay will host a conference call today at 4:30 p.m. ET to discuss fourth quarter and fiscal year end 2019 financial results and provide a business update. To access the live conference call, please dial 855-327-6837 from the U.S. and Canada, or 631-891-4304 internationally, Conference ID# 10008868. To access the live and subsequently archived webcast of the conference call, go to the Investors section of the company’s website at View Source