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]).

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!

"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.

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.

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 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 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer, autoimmune/inflammatory, and other diseases, today presented new preclinical data on ALPN-202, a conditional CD28 costimulator and dual checkpoint inhibitor for the treatment of advanced malignancies, at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 34th Annual Meeting (Press release, Alpine Immune Sciences, NOV 8, 2019, View Source [SID1234550761]). ALPN-202 is Alpine’s lead oncology program and remains on track to initiate a first-in-human clinical trial by the first quarter of 2020.

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!

ALPN-202 is designed to improve upon the safety and efficacy of existing combination checkpoint and/or costimulation therapeutic strategies. One poster presents mechanistic data supporting that ALPN-202 inhibits both the PD-L1 and CTLA-4 checkpoint pathways while also providing PD-L1-dependent CD28 costimulation, as intentionally designed. A second poster demonstrates the ability of ALPN-202 to improve significantly upon the activity of existing cancer therapeutics when given alone and/or in combination in preclinical models. In addition, crystallographic study suggests that ALPN-202 binds PD-L1 and CD28 at distinct, non-overlapping epitopes enabling its potentially unique functionality:

P793. ALPN-202, a Conditional CD28 Costimulator and Dual Checkpoint Inhibitor, Utilizes Multiple Mechanisms to Elicit Potent Anti-Tumor Immunity Superior to Checkpoint Blockade

P467. ALPN-202, a Conditional CD28 Costimulator and Dual Checkpoint Inhibitor, Enhances the Activity of Multiple Standard of Care Modalities

Immune checkpoint inhibitors targeting the PD-1/PD-L1 and/or CTLA-4 pathways have demonstrated clinical activity in multiple cancers, but many patients still experience inadequate anti-tumor responses and/or relapse, which may be in part due to insufficient anti-tumor T cell activation and/or exhaustion. At the same time, combinations of checkpoint inhibitors and/or costimulatory agents can result in excessive immune-related toxicities. "ALPN-202 is engineered to address both of these issues by promoting T cell activity, but primarily only in a tumor-specific fashion, to produce specific, durable anti-tumor immune responses," said Stanford Peng, MD PhD, Alpine’s President and Head of Research and Development. "These data continue to encourage us regarding the potential for ALPN-202 as a new, first-in-class cancer immunotherapy. We continue to look forward to initiating our first clinical trial of ALPN-202."

The full poster presentations can be found at: View Source and View Source

About ALPN-202

ALPN-202 is a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor, which has the potential to improve upon the efficacy of combined checkpoint inhibition while limiting significant toxicities. Preclinical studies of ALPN-202 have successfully demonstrated superior efficacy in tumor models compared to checkpoint inhibition alone. We anticipate initiation of the first-in-human clinical study of ALPN-202 to begin by the first quarter of 2020.

On November 8, 2019 Rubius Therapeutics, Inc. (Nasdaq: RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines, reported that the Company presented preclinical data supporting its lead artificial antigen presenting cell program, RTX-321, for the potential treatment of HPV 16-positive tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting (Press release, Rubius Therapeutics, NOV 8, 2019, View Source [SID1234550760]). Last month at the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference on Molecular Targets and Cancer, Rubius Therapeutics presented data demonstrating that its Red Cell Therapeutics can be engineered to create a loadable system for personal neoantigens, unlocking a potential new use of our RED PLATFORM.

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!

"Current cell therapy approaches are limited by a number of challenges – they require harvesting and engineering a patient’s own T cells, undergo a lengthy manufacturing process, are limited in the number of targets that can be pursued, and, once administered to patients, can elicit unpredictable immune responses, including severe side effects. Today at SITC (Free SITC Whitepaper), we presented additional preclinical proof of concept data demonstrating that Rubius Therapeutics can engineer allogeneic artificial antigen presenting cells against a tumor-associated antigen that significantly expand antigen-specific T cells and nearly eliminates lung metastases in a melanoma mouse model with minimal, reversible toxicity," said Pablo J. Cagnoni, M.D., chief executive officer of Rubius Therapeutics. "Separately, current personalized neoantigen approaches are promising, but do not adequately stimulate and expand the right subset of T cells to the levels required to achieve robust efficacy. Last month at AACR (Free AACR Whitepaper)-NCI-EORTC, Rubius Therapeutics presented data showing that we can engineer our red cells to create a loadable system for personal neoantigens and dramatically expand primary T cells to induce an immune response, unlocking a potential new use of our RED PLATFORM."

Data Summaries

Red Cell Therapeutic Artificial Antigen Presenting Cells (aAPCs) at SITC (Free SITC Whitepaper)

(P233) RTX-321, an Allogeneic Artificial Antigen Presenting Red Cell Therapeutic, Expressing MHC I-Peptide, 4-1BBL and IL-12, Promotes Antigen-Specific T Cell Expansion and Anti-Tumor Activity in HPV16+ Tumors

Allogeneic Red Cell Therapeutic artificial antigen presenting cells (RTX-aAPCs) are engineered to induce a tumor-specific response by expanding antigen-specific T cells.
As preclinical proof of concept, mouse red cells were chemically engineered with hundreds of thousands of copies of the major histocompatibility complex (MHC) I loaded with the gp100 peptide, a melanoma antigen, 4-1BBL and IL-12 on the cell surface and were tested in a B16-F10 melanoma mouse model.
These cells (mRBC-gp100-4-1BBL-IL-12 ) nearly eliminated lung metastases at the highest dose levels.
mRBC-gp100-4-1BBL-IL-12 promoted gp100-specific T cell expansion in the circulation, secondary lymphoid organs and lungs.
RTX-aAPC was engineered with a cytomegalovirus (CMV) antigen, 4-1BBL and IL-12 and expanded CMV-specific T cells from healthy donor peripheral blood mononuclear cells (PBMCs).
RTX-321 (HPV+) was engineered to express an HPV peptide antigen bound to MHC I, 4-1BBL and IL-12 on the cell surface to mimic human T cell-APC interactions.
Expression of IL-12 as signal 3 on an aAPC resulted in more robust antigen-specific T cell expansion, memory formation and cytotoxicity against tumor cells when compared to IL-7 or IL-15, leading the Company to select IL-12 as signal 3 for RTX-321.
RTX-321 is selectively directed against an HPV dominant epitope and promoted T cell receptor (TCRs), 4-1BB and IL-12 receptor signaling in engineered cell lines.
RTX-321 expanded HPV-specific TCR-transduced primary human T cells.
RTX-321 is currently in IND-enabling studies.
Loadable Red Cell Therapeutic Artificial Antigen Presenting Cells for Neoantigens at AACR (Free AACR Whitepaper)-NCI-EORTC

(B062) Enabling the Rapid Generation of Allogeneic Artificial Antigen Presenting Cell (aAPC) Red Cell Therapeutics with a Loadable MHC System

Allogeneic Red Cell Therapeutic artificial antigen presenting cells (RTX-aAPCs) are engineered to induce an tumor-specific response by expanding antigen-specific T cells.
A loadable MHC system was engineered to enable the rapid generation of aAPCs targeting personal neoantigens.
Antigenic peptides can be loaded onto empty MHC constructs, which can be stably expressed at high levels.
RTX-aAPCs with peptide-loaded MHC constructs functionally engaged TCRs and achieved robust expansion of primary CMV-specific T cells in healthy donor PBMCs with prior exposure to CMV.
Rubius Therapeutics’ loadable aAPC system has the potential to generate aAPCs containing multiple neoantigens in a single therapeutic.
Further development of a loadable aAPC system may enable effective personalized neoantigen therapies.

On November 8, 2019 Exact Sciences Corp. (NASDAQ: EXAS) reported that it has completed its previously announced combination with Genomic Health, Inc. (NASDAQ: GHDX) (Press release, Exact Sciences, NOV 8, 2019, View Source [SID1234550759]).

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!

"Today marks a pivotal step toward building the world’s leading advanced cancer diagnostics company," said Kevin Conroy, chairman and CEO of Exact Sciences. "We’re excited to bring together some of the greatest minds in cancer diagnostics and continue to deliver advanced tests to providers and patients along their cancer journey. With a best-in-class R&D, clinical, and commercial organization and a global infrastructure, we are well positioned to increase adoption of our existing tests and accelerate the development and launch of future cancer diagnostics. I welcome the talented Genomic Health employees to the Exact Sciences family and look forward to leading our combined team as we enter our Company’s next chapter."

As a result of the transaction’s close, Genomic Health’s common stock will now cease to be traded on the NASDAQ.