On November 8, 2019 Forbius, a clinical-stage protein engineering company that develops biotherapeutics to treat fibrosis and cancer,reported the first Phase 1 clinical data from its oncology development program with AVID200, in a late-breaking poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting 2019 in National Harbor, Maryland (Nov. 6-10) (Press release, Forbius, NOV 8, 2019, View Source [SID1234550745]).

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AVID200 is a first-in-class, selective inhibitor of TGF-beta 1 & 3, the main pathogenic TGF-beta isoforms. AVID200 spares TGF-beta 2 for optimal safety.

The AVID200-03 trial (NCT03834662) is an open label, multicenter, dose-escalation study of AVID200 monotherapy following a standard 3 + 3 design in patients with advanced or metastatic solid tumor malignancies and no other treatment options.

In the presentation entitled "AVID200, first-in-class TGF-beta 1 and beta 3 selective inhibitor: Results of a Phase 1 monotherapy dose escalation study in solid tumors and evidence of target engagement in patients (Abstract # P856)", Dr Timothy Yap, Associate Professor, MD Anderson Cancer Center, and a PI in the trial detailed the following:

A total of 15 patients received AVID200 at 5, 15 and 30 mg/kg once every three weeks, 4 patients remain ongoing at time of data presentation.
AVID200 achieved dose-proportional exposure and exhibited peripheral target inhibition of TGF-beta 1 & 3 over the entire dosing period at all dose levels tested.
AVID200 was well-tolerated and the maximum tolerated dose (MTD) was not reached.
No patients at either of the two higher dose levels, 15 mg/kg (550 mg/m2) and 30 mg/kg (1100 mg/m2), had any toxicities greater than Grade 2.
A single patient with appendiceal carcinoma who had a prior total colectomy and was treated in the lowest dose level cohort (5 mg/kg / 180 mg/m2), experienced grade 3 (G3) events including G3 diarrhea (worsening from G2 diarrhea at enrolment) which was characterized as the only DLT in the trial.
Several patients experienced stable disease including one patient with prolonged stable disease of more than 8 months who continues on treatment.
Ilia Tikhomirov, CEO of Forbius, commented: "With this Phase 1a dose-escalation study we have shown that selective inhibition of TGF-beta isoforms 1 & 3 via AVID200 leads to efficient blockade of the TGF-beta pathway with potentially best-in-class tolerability. We look forward to reporting additional clinical data from across the AVID200 program."

About TGF-beta 1 & 3

TGF-beta 1 & 3 are the main oncogenic TGF-beta isoforms expressed by many solid tumors. They are believed to play a major role in T-cell suppression, fibrosis and resistance to anti-PD-(L)1 therapies such as nivolumab (Opdivo) and pembrolizumab (Keytruda) (Chakravarthy, Nature Comm., 2018; Tauriello, Nature, 2018; Mariathasan, Nature, 2018).

About AVID200 and the AVID200-03 Trial (NCT03834662)

AVID200 is an isoform-selective and highly potent inhibitor of TGF-beta 1 & 3 undergoing Phase 1 clinical testing in solid tumors and fibrotic diseases. TGF-beta 1 & 3 are the principal disease-driving isoforms, while TGF-beta 2 is responsible for normal cardiac function and hematopoiesis.

AVID200’s selectivity for TGF-beta 1 & 3 was designed to achieve optimal efficacy while circumventing cardiac and other safety issues that have limited the applicability of earlier-generation, non-selective TGF-beta inhibitors. Therefore, AVID200 is positioned to be an effective and well-tolerated therapeutic in a variety of clinical settings, including in combination with anti-PD-(L)1 therapy.

AVID200-03 (NCT03834662) is an open label, multicenter, dose-escalation study to evaluate the safety, pharmacokinetics, pharmacodynamics and antitumor effects of AVID200 in patients with advanced or metastatic solid tumor malignancies.

About Forbius: Targeting TGF-beta and EGFR Pathways in Fibrosis and Cancer

Forbius is a clinical-stage protein engineering company that develops biotherapeutics to treat fibrosis and cancer. We are focused on the transforming growth factor-beta (TGF-beta) and epidermal growth factor receptor (EGFR) pathways.

Forbius’ team of TGF-beta biology experts designed a proprietary platform of TGF-beta inhibitors with best-in-class potency and selectivity against the principal disease-driving isoforms 1 & 3. This novel class of TGF-beta inhibitors has proven highly active in preclinical models of fibrosis and cancer and was well-tolerated in long-term toxicology studies. Forbius’ lead TGF-beta 1 & 3 inhibitor, AVID200, is undergoing Phase 1 clinical trials in two fibrotic indications as well as in solid tumors.

Forbius’ lead program targeting EGFR is AVID100. AVID100 is an anti-EGFR antibody-drug conjugate (ADC) with a novel tumor-selective mode of action. This program is undergoing Phase 2a clinical trials in EGFR-overexpressing solid tumors.

On November 8, 2019 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers, reported a poster showing preclinical data from its natural killer (NK) cell chimeric antigen receptor (CAR) program at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in National Harbor, Md (Press release, Bellicum Pharmaceuticals, NOV 8, 2019, View Source [SID1234550762]). The poster titled "Solid Tumor Cytotoxicity by Natural Killer Cells Expressing a HER2-Directed Chimeric Antigen Receptor Enhanced by MyD88/CD40 (MC)" presented preclinical data demonstrating the effects of MC signaling on NK cell anti-tumor potency.

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The poster presented preclinical data using MyD88/CD40 (MC) cell signaling to enhance innate NK cell function, including augmented cytotoxicity and cytokine production against multiple tumor cell lines. MC signaling also improved in vitro and in vivo NK cell proliferation when coupled with autocrine IL-15 production. Co-expression of an antigen-specific CAR together with the MC/IL-15 system further increased anti-tumor efficacy against hematological and solid tumor targets. MC-augmented GoCAR-NK cells could represent a potent off-the-shelf cell therapy for the treatment of cancer.

On November 8, 2019 Actym Therapeutics, a privately held biotechnology company focused on therapeutic targeting of intractable immune pathways in the tumor microenvironment, reported that it will be presenting data at the SITC (Free SITC Whitepaper) Annual Meeting in National Harbor, Maryland on November 9, 2019 (Press release, Actym Therapeutics, NOV 8, 2019, View Source [SID1234550778]). The presentation is entitled "STACT: A Novel Therapeutic Platform that Delivers Immunomodulatory Payloads to Tumor-Resident Myeloid Cells After IV Dosing and Demonstrates Potent Anti-Tumor Efficacy in Preclinical Studies".

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"Therapeutic targeting of many immune pathways is currently limited to a suboptimal, intratumoral (IT) route of administration. This is due to toxicities or lack of efficacy when systemically dosed, and will not be tractable in a metastatic disease setting. Using our tumor-specific therapeutic platform, our data will show strong anti-tumor effects, including single agent cures, after IV dosing with genetic payloads encoding highly immunomodulatory proteins. Furthermore, we will show that STACT permits the combinatorial administration of payloads that would otherwise be too toxic if systemically administered. When IV dosed, our therapies are able to infiltrate and enrich in solid tumors and be consumed by tumor resident cells, delivering genetic payload-encoding plasmids. This allows for ectopic expression of a wide range of multiplexed immunomodulatory proteins in a tumor-specific manner. We are encouraged by the preclinical data demonstrating single-agent cures against checkpoint-refractory, orthotopic, highly metastatic breast cancer tumors," said Dr. Christopher Thanos, President and CEO of Actym Therapeutics.

Details of the presentations are as follows:

Abstract #

Title

P482

STACT: A Novel Therapeutic Platform that Delivers Immunomodulatory Payloads to Tumor-Resident Myeloid Cells After IV Dosing and Demonstrates Potent Anti-Tumor Efficacy in Preclinical Studies

Location: Gaylord Conference Center, National Harbor, MD

For those unable to attend the conference who would like a copy of the presentation, please send an email request to [email protected]. Please include your name, company, title and phone number. The presentation will be emailed to those making proper requests after November 9, 2019.

On November 8, 2019 BioSpecifics Technologies Corp. (NASDAQ: BSTC), a biopharmaceutical company that originated and continues to develop collagenase-based therapies with a first in class collagenase-based product marketed as XIAFLEX in the U.S. and Xiapex in Europe, reported its financial results for the third quarter ended September 30, 2019 and provided a corporate update (Press release, BioSpecifics Technologies, NOV 8, 2019, View Source [SID1234550746]).

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"As we approach the end of 2019, BioSpecifics is entering its next phase of growth as we seek to unlock new opportunities to generate value for all our stakeholders," said J. Kevin Buchi, chief executive officer of BioSpecifics. "We are excited by the prospect of adding a third marketed XIAFLEX indication to our commercial pipeline with the potential FDA approval of CCH for the treatment of cellulite. BioSpecifics today is a profitable, commercial-stage organization with a diverse development pipeline focused on CCH and the team is eager to build on this trajectory."

Third Quarter 2019 Financial Results

BioSpecifics reported net income of $6.3 million for the third quarter ended September 30, 2019, or $0.86 per basic share and $0.85 per share on a fully diluted basis, compared to net income of $5.0 million, or $0.69 per basic share and $0.69 per share on a fully diluted basis, for the same period in 2018.

Total revenue for the third quarter ended September 30, 2019 was $9.4 million, compared to $8.2 million for the same period in 2018. The increase in total revenues for the quarterly period was primarily due to royalties associated with higher net sales of XIAFLEX in Peyronie’s Disease and Dupuytren’s Contracture.

Research and development expenses for the third quarter ended September 30, 2019 were $0.1 million compared to $0.2 million for the same period in 2018.

General and administrative expenses for the third quarter ended September 30, 2019 were $2.0 million, compared to $2.2 million for the same period in 2018.

Provision for income taxes for the third quarter ended September 30, 2019 were $1.6 million, compared to $1.1 million for the same period in 2018.

As of September 30, 2019, BioSpecifics had cash and cash equivalents and investments of $98.4 million, compared to $82.0 million as of December 31, 2018.

As of September 30, 2019, BioSpecifics had 7,343,119 million shares of common stock outstanding.

Commercial & Pipeline Highlights

BioSpecifics’ Royalty Revenues from the XIAFLEX Commercial Franchise Grew by 15% Year-Over-Year for the Third Quarter of 2019: XIAFLEX revenue growth was primarily attributable to royalties associated with higher net sales of XIAFLEX in Dupuytren’s Contracture and Peyronie’s Disease.
BLA filing for CCH for Treatment of Cellulite Submitted in September 2019: On September 6, 2019, Endo announced that it filed its Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) for CCH for the treatment of cellulite.
New XIAFLEX Data Presented at the 20th Annual Fall Meeting of the Sexual Medicine Society of North America: In October 2019, Endo announced that five new studies of XIAFLEX for the treatment of Peyronie’s Disease were presented at the 20th Annual Fall Meeting of the Sexual Medicine Society of North America (SMSNA) which continue to support further patient and physician education.
New Data Presented on MRI Evaluation of Cellulite at the American Society for Dermatologic Surgery Annual Meeting: In October 2019, Endo announced the presentation of a case study comparison of the use of a standing MRI versus a prone MRI for the evaluation of cellulite. The comparison results showed a <10° difference between the angle of collagen septae orientation relative to the dermis in the standing and prone MRI. Septae orientation in the prone position was not perpendicular to the skin.
Corporate Highlights

Appointment of New Chief Executive Officer: In October 2019, BioSpecifics announced the appointment of J. Kevin Buchi as Chief Executive Officer, bringing the company diversified leadership experience, coupled with a strong life sciences background.
Appointment of Jennifer Chao as Chairman of Board of Directors: In October 2019, BioSpecifics announced the appointment of Jennifer Chao as chairman of the board of directors, who previously served as an independent director of the board since 2015.

On November 8, 2019 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation oncology therapeutics, reported its financial results for the three and nine months ended September 30, 2019 (Press release, Sutro Biopharma, NOV 8, 2019, View Source [SID1234550763]).

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"In late October 2019, we presented encouraging interim safety data from our Phase 1 trial for STRO-002 at the AACR (Free AACR Whitepaper)-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference, as we further advance our pipeline of product candidates and programs," said Bill Newell, Sutro’s Chief Executive Officer. "STRO-002 is our second proprietary ADC in clinical trials, and one of four ADC clinical product candidates from our platform in the past three years, including those of our collaborators. We believe our proprietary technology allows us to rapidly and precisely create optimally designed, next-generation protein therapeutics candidates for cancer and autoimmune disorders."

Recent Business Highlights and Developments

STRO-001 Clinical Program

Potential first-in-class and best-in-class Antibody Drug Conjugate ("ADC") directed against CD74, which is highly expressed in many B cell malignancies.
Phase 1 dose-escalation with dose expansion; clinical trial enrolling patients with multiple myeloma and non-Hodgkin lymphoma, with initial safety data presented at the EHA (Free EHA Whitepaper) Congress in June 2019. Safety data with several additional patients was released in an abstract in association with the American Society of Hematology (ASH) (Free ASH Whitepaper) Conference on November 6, 2019.
STRO-002 Clinical Program

Potential best-in-class ADC directed against folate receptor-alpha, which is highly expressed in ovarian cancer.
Phase 1 dose-escalation, with dose expansion, clinical trial enrolling women with advanced ovarian and endometrial cancers, with initial safety data presented at the AACR (Free AACR Whitepaper)-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference on October 29, 2019.
STRO-002 was well tolerated in patients with advanced relapsed and refractory ovarian cancer and demonstrated preliminary evidence of anti-tumor activity.
No ocular toxicity has been observed in the trial to date.
Potent anti-tumor activity was seen in preclinical endometrial cancer models.
BCMA ADC Clinical Program

Celgene received FDA clearance on its IND application CC- 99712 targeting B-cell maturation antigen ("BCMA") for the treatment of multiple myeloma in the second quarter of 2019. This is the third product candidate to originate from Sutro’s proprietary discovery and manufacturing platform to enter clinical development since early 2018, and for which Celgene has worldwide development and commercialization rights. Sutro is entitled to development and regulatory milestone payments and tiered royalties ranging from mid to high single digit percentages from Celgene for this BCMA ADC.
Bispecific ADC Clinical Development Candidate

In the third quarter of 2019, Merck KGaA, Darmstadt, Germany designated an undisclosed bispecific ADC as a clinical development candidate with approval to advance to IND-enabling studies, which triggered a financial milestone to be received by Sutro. As part of the agreement, Sutro will manufacture the ADC for the early clinical supply of the candidate and is eligible for further milestones and royalties. Merck KGaA, Darmstadt, Germany will be responsible for drug product, clinical development and commercialization of this clinical development candidate.
Third Quarter 2019 Financial Highlights

Cash, Cash Equivalents and Marketable Securities

As of September 30, 2019, Sutro had cash, cash equivalents and marketable securities of $150.4 million, as compared to $204.5 million as of December 31, 2018, which represents net cash usage of $17.8 million and $54.1 million during the three and nine months ended September 30, 2019, respectively.

Revenue

Revenue was $12.3 million and $31.4 million for the three and nine months ended September 30, 2019, respectively, compared to $7.8 million and $19.3 million for the same periods in 2018. On January 1, 2019, Sutro adopted Accounting Standards Update No. 2014-09 Revenue from Contracts with Customers (Accounting Standards Codification Topic 606). For more information on the impact of the adoption of the new revenue standard, see "Notes to Unaudited Interim Condensed Financial Statements" contained in Part I, Item 1 of Sutro’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 7, 2019. Future collaboration revenue from Celgene, Merck and EMD Serono, and from any future collaboration partners, will fluctuate as a result of the amount and timing of revenue recognition of upfront, milestones and other collaboration agreement payments.

Operating Expenses

Total operating expenses for the three and nine months ended September 30, 2019, were $25.0 million and $72.1 million, respectively, compared to $18.0 million and $53.3 million for the same periods in 2018, including non-cash stock-based compensation of $2.9 million and $0.3 million, and depreciation and amortization expense of $1.2 million and $1.1 million, in the 2019 and 2018 third quarters, respectively. Total operating expenses for third quarter 2019 were comprised of research and development expenses of $16.9 million and general and administrative expenses of $8.1 million, with both expense types expected to increase in 2019 as Sutro’s internal product candidates advance in clinical development and additional general and administrative expenses are incurred as a public company.