On March 26, 2020 -BiomX Inc. (NYSE: PHGE), a clinical-stage biotechnology company developing both natural and engineered phage therapies that target specific pathogenic bacteria, reported financial results and provided a business update for the full year ended December 31, 2019 (Press release, BiomX, MAR 26, 2020, View Source [SID1234555880]).

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"2019 was a landmark year for BiomX as we advanced our lead program in acne-prone individuals into the clinic and, through our merger, listed publicly on the NYSE American stock exchange," said Jonathan Solomon, BiomX Chief Executive Officer. "Phage can target and kill specific bacteria. This property, combined with an excellent safety record, creates the potential for it to become a disruptive therapeutic modality for the treatment of chronic diseases in which bacteria play a causative role. With our phage cocktail customization capabilities, cutting-edge synthetic biology, computational biology tools, phage manufacturing facilities and a strong financial position, we believe we are well positioned to leverage phages’ unique potential and develop important and novel therapeutics. We continue to be on track to announce data from our Phase 1 study of our lead candidate BX001 in subjects with acne prone skin at the end of the first quarter of 2020 and Phase 1 data for our inflammatory bowel disease program in the fourth quarter of 2020."

COVID-19 Update

In light of the evolving COVID-19 pandemic, BiomX has implemented all recommended measures to safeguard the health and safety of its employees and the continuity of its business operations. The Company’s research and development programs currently remain on schedule. In addition BiomX enjoys a strong cash position with over $82 million in cash, cash equivalents and short-term deposits as of the end of 2019.

Recent Highlights

Development Programs

Completed enrollment of a Phase 1 cosmetic clinical study in subjects with acne-prone skin. BiomX completed enrollment in a first-in-human cosmetic clinical study of BX001 in 75 subjects with mild to moderate acne. BX001 is a topically administered gel comprised of a cocktail of naturally occurring phage designed to address the appearance of acne by targeting Cutibacterium acnes (or C. acnes, formerly taxonomically classified as P. acnes), a bacterium implicated in the pathophysiology of acne vulgaris.
Pre-IND meeting held with FDA and manufacturing initiated for BX002 for the treatment of Inflammatory Bowel Disease (IBD). BX002 is a phage cocktail targeting strains of Klebsiella pneumoniae that have been shown in animal models to be pro-inflammatory and pathogenic and may have a role in the onset and aggravation of the disease in humans1. BiomX has advanced towards the clinic with a pre-Investigational New Drug (IND) regulatory meeting and initiated manufacturing for clinical trials in this indication.
Presented preclinical results from program targeting Primary Sclerosing Cholangitis (PSC) at AASLD conference. BiomX presented in vivo data on a phage cocktail that substantially reduced bacterial burden of pathogenic Klebsiella pneumoniae strains which are thought to be disease modifying in PSC, a rare progressive liver disorder with no FDA-approved treatment2.
Presented preclinical results from colorectal cancer program at AACR (Free AACR Whitepaper) Microbiome, Viruses, and Cancer Conference. BiomX presented preclinical in vivo data on phage that target Fusobacterium nucleatum, a bacterium present in the microenvironment of colorectal cancer tumors and thought to protect tumors from the host’s immune system3. BiomX also successfully applied synthetic engineering to convert phage from temperate (lysogenic) to lytic, the state in which phage kill bacteria.
Completed construction of in-house phage manufacturing facility. The new facility, located at the Company’s headquarters, supports clinical manufacturing of candidate phage products and in the future could be expanded to support commercial manufacturing needs.
Corporate

Successfully completed merger resulting with a NYSE American stock exchange public listing and significant capital. In October 2019, BiomX announced closing of the merger with Chardan Healthcare Acquisition Corp. with $60.1 million raised.
Announced dual listing on the Tel-Aviv Stock Exchange (TASE). In February 2020, the Company’s common stock began public trading on the TASE.
Announced additions to Board of Directors and Senior Management. BiomX announced the addition of Russell G. Greig, Ph.D., as Chairman and Lynne Sullivan as Director to the BiomX Board and Chair of the Audit Committee. On October 2019, Merav Bassan, Ph.D., was appointed Chief Development Officer.
Key Upcoming Milestones

Data from the phase 1 cosmetic clinical study of BX001 in subjects with acne-prone skin to be announced at the end of the first quarter of 2020. The primary endpoints of the randomized, double-blind, dose-ranging, vehicle-controlled study are safety and tolerability. Exploratory endpoints include proof of principle by measurement of the effect of BX001 on C. acnes levels.
Data from the phase 1 study of BX002 in inflammatory bowel disease to be announced in the fourth quarter of 2020.
Engineering F. nucleatum phage with various payloads (such as immunostimulatory payloads) and initiating proof of concept in animal models by the fourth quarter of 2020.
Full Year 2019 Financial Results

Cash balance and short-term deposits as of December 31, 2019, were $82.3 million, compared to $40 million as of December 31, 2018. The increase was mainly due to funds raised through completion of the merger with Chardan Healthcare Acquisition Corp.
Research and development expenses of $13.5 million in 2019, compared to $9.1 million in 2018. The increase was attributed mostly to the manufacturing of BX001 and BX002, the Company’s product candidates for acne-prone skin, and IBD, respectively, and due to initiation of the BX001 clinical study.
General and administrative expenses of $8.7 million in 2019, compared to $3.4 million in 2018, mainly due to merger-related expenses and construction of the Company’s in-house manufacturing facility.
Net loss of $20.6 million in 2019, compared to $12.7 million in 2018.
Net cash used in operating activities of $17.6 million in 2019, compared to $11.3 million in 2018.
1 Atarashi et al. (2017), Science
2 Nakamoto et al. (2019), Nature Microbiology
3 Bullman et al. (2017), Science

About Phage Therapy

Bacteriophage, or phage, are viruses that target bacteria and are considered inert to mammalian cells. Phage are designed to target and kill specific bacterial species or strains without disrupting other bacteria or the healthy microbiota. All of BiomX’s phage-based product candidates derive from its proprietary platform, which is first used to discover and validate the association of specific bacterial strains with human diseases or conditions, and is then used to develop rationally-designed phage combinations ("cocktails") of naturally occurring or synthetic phage to target pathogenic bacteria. The phage cocktails contain multiple phage with complementary functions optimized through in vitro and in vivo testing.

On March 26, 2020 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company focused on creating and developing engineered IgM antibodies, reported its financial results for the fourth quarter and full year ended December 31, 2019 and provided an update on recent developments (Press release, IGM Biosciences, MAR 26, 2020, View Source [SID1234555865]).

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"2019 was a transformational year for IGM. The many highlights of the year included our successful initial public offering and the initiation of our first-in-human trial for our lead product candidate, IGM-2323, a CD20 x CD3 bispecific IgM antibody, in patients with relapsed/refractory non-Hodgkin’s lymphoma (NHL)," said Fred Schwarzer, Chief Executive Officer of IGM Biosciences. "We expect continued progress in 2020, with the filing of an Investigational New Drug application (IND) with the Food and Drug Administration (FDA) for our second product candidate, IGM-8444 and the presentation of initial data from our clinical trial of IGM-2323. With thanks to the IGM team, we believe we are well positioned to remain the global leader in the research and development of engineered therapeutic IgM antibodies."

Recent Highlights and Pipeline Updates

IGM-2323 – Phase 1 trial initiated: In October 2019, IGM announced dosing of the first patient in its Phase 1 clinical trial evaluating IGM-2323 in patients with relapsed/refractory B cell NHL. This Phase 1 clinical trial represents the first-in-human application of IGM Biosciences’ engineered IgM antibody technology. IGM expects to report initial data from this Phase 1 trial in the second half of 2020.

IGM-8444 – IND filing planned: IGM expects to file an IND application with the FDA for IGM-8444 in 2020, initially for the treatment of patients with solid tumors. IGM-8444 is an IgM antibody targeting the Death Receptor 5 (DR5) protein, which is broadly expressed on a broad range of solid and hematologic malignancies.

IGM-7354 – Next candidate announced: IGM nominated IGM-7354 as its third clinical candidate. IGM-7354 is a targeted IL-15 immune stimulating antibody which demonstrates another use of IGM’s novel J chain based bispecific technology. In this case, the immune stimulating IL-15 is displayed on the J chain of an anti-PD-L1 IgM antibody, which serves to display the immune stimulating IL-15 on the surface of PD-L1 positive cells, such as cancer cells. IGM expects to file an IND with the FDA for IGM-7354 in 2021.

Fourth Quarter and Full Year 2019 Financial Results

Cash and Investments: Cash and investments as of December 31, 2019 were $236.6 million.

Research and Development (R&D) Expenses: For the fourth quarter and year ended 2019, R&D expenses were $12.8 million and $35.3 million, respectively.
General and Administrative (G&A) Expenses: For the fourth quarter and year ended 2019, G&A expenses were $3.2 million and $9.2 million, respectively.
Net Loss: For the fourth quarter of 2019, net loss was $14.8 million, or a loss of $0.49 per share. For the year ended 2019, net loss was $43.1 million, or a loss of $4.80 per share.
Shares Outstanding: Weighted-average shares outstanding for the fourth quarter of 2019 were 30.5 million and for the full year of 2019 were 9.0 million shares.
2020 Financial Guidance

IGM estimates non-GAAP operating expenses for 2020 of approximately $75 – $85 million, excluding estimated non-cash stock-based compensation expense of approximately $8 million. Including non-cash stock-based compensation expense, IGM estimates GAAP operating expenses for 2020 of $83 – $93 million. IGM also expects to end 2020 with a balance of over $140 million in cash and investments.

Conference Call and Webcast

IGM will host a conference call and webcast to discuss this announcement today, March 26, at 4:30 p.m. ET. To access the live call by phone please dial (866) 649-1996 (domestic) or (409) 217-8769 (international); the conference ID is 2991398. A live audio webcast of the event may also be accessed through the "Investors" section of IGM’s website at www.igmbio.com. A replay of the webcast will be available for 30 days following the event through 11:59p.m. ET on April 25, 2020.

On March 26, 2020 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported the publication of a multicenter, prospective study demonstrating that DecisionDx-UM test results significantly impacted treatment plan recommendations for patients with uveal melanoma (UM) (Press release, Castle Biosciences, MAR 26, 2020, View Source [SID1234555881]). The study was published in the peer-reviewed journal Melanoma Management.

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DecisionDx-UM is Castle’s 15-gene expression profiling (GEP) test developed to identify patients at low risk (Class 1) or high risk (Class 2) of metastasis, based on the unique biology of their primary tumor, and is current standard of care for uveal melanoma patients. It is estimated that nearly 8 in 10 patients diagnosed with uveal melanoma in the U.S. receive the DecisionDx-UM test as part of their diagnostic workup.

The multicenter CLEAR II study (Clinical Application of DecisionDx-UM Gene Expression Assay Results II) was designed to prospectively evaluate patterns of physician referral and metastatic surveillance regimens for UM patients who were tested with DecisionDx-UM as part of their diagnostic work up, and to compare management plans between DecisionDx-UM low-risk (Class 1) and DecisionDx-UM high-risk (Class 2) patients.

"The results from the CLEAR II study demonstrate that the DecisionDx-UM test has a significant impact on treatment plan recommendations for patients with uveal melanoma," said first author Amy C. Schefler, M.D., Associate Professor of Clinical Ophthalmology, Weill Cornell Medical College/Houston Methodist Hospital and the University of Texas Health Science Center at Houston, and Retina Consultants of Houston. "DecisionDx-UM stratifies patients, based on tumor biology, into high- and low-risk groups, and this study demonstrates that physicians developed appropriate, risk-aligned treatment plans based on this genomic information."

Study Highlights:

138 patients from nine centers were enrolled in the CLEAR II study.
93 patients (67%) had a low-risk Class 1 test result; and 45 patients (33%) had a high-risk Class 2 test result. This ratio is consistent with clinical experience (in 2019, 68% of all test results were Class 1, and 32% were Class 2 test results).
Medical oncology referral was more common for high-risk Class 2 patients than for low-risk Class 1 patients (p<0.001).
Class 1 patients were less likely to have their metastatic surveillance managed by a medical oncologist compared to Class 2 patients (p<0.001).
Patients with a Class 1 result were significantly less likely to receive recommendations for frequent (three or four times a year) surveillance imaging and liver function testing compared to Class 2 patients (p<0.001).
These findings show that treatment plan recommendations are aligned with metastatic risk and are consistent with results from previously published studies documenting the impact of DecisionDx-UM on patient management.
About DecisionDx-UM

DecisionDx-UM is a 15-gene expression profiling (GEP) test that uses an individual patient’s tumor biology to predict individual risk of metastasis. DecisionDx-UM is considered to be standard of care in the management of uveal melanoma in the majority of ocular oncology practices in the United States. Since 2009, the American Joint Committee on Cancer (AJCC; v7 and v8) Staging Manual for UM has specifically identified the GEP test as a prognostic factor that is recommended for collection as a part of clinical care. Further, the National Comprehensive Cancer Network (NCCN) guidelines for uveal melanoma include the DecisionDx-UM test result as a prognostic method for determining risk of metastasis and recommended differential surveillance regimens based on a Class 1A, 1B, and 2 result. DecisionDx-UM is the only prognostic test for uveal melanoma that has been validated in prospective, multi-center studies, and it has been shown to be a superior predictor of metastasis compared to other prognostic factors, such as chromosome 3 status, mutational status, AJCC stage and cell type.

It is estimated that nearly 8 in 10 patients diagnosed with uveal melanoma in the U.S. receive the DecisionDx-UM test as part of their diagnostic workup. More information about the test and disease can be found at www.MyUvealMelanoma.com.

On March 26, 2020 Apollo Endosurgery, Inc. ("Apollo") (Nasdaq: APEN), a global leader in less invasive medical devices for gastrointestinal and bariatric procedures, reported financial results for the fourth quarter and year ended December 31, 2019 (Press release, Apollo Endosurgery, MAR 26, 2020, View Source [SID1234555866]). The Company will hold a conference call today at 3:30 p.m. CT / 4:30 p.m. ET to discuss its results.

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Highlights
•Fourth quarter U.S. OverStitch Endoscopic Suturing System ("ESS") sales increased 33% to $4.4 million
•Fourth quarter U.S. Endoscopy sales increased 31% to $5.6 million
•Worldwide ESS sales for the full year 2019 increased 21% (23% in constant currency) to $28.3 million, representing 63% of our Endoscopy sales
•Fourth quarter Orbera Intragastric Balloon System ("IGB") sales increased 23% in the U.S. and 11% (13% in constant currency) worldwide
Todd Newton, CEO of Apollo, said, "The Endoscopic Suturing market developed rapidly in 2019 as evidenced by Apollo’s 36% revenue growth for ESS products in the U.S. and 21% growth worldwide. Clinical publications providing evidence of the many applications for our ESS technology continued to expand during 2019, and Apollo’s new single channel OverStitch device introduced in November 2018 is taking our technology to a broader group of physicians and locations. Our strategy in the near term is to withstand the unprecedented challenges presented by the COVID-19 pandemic, and then return our focus as swiftly as possible to increasing the user base of our technology and to improve our operating efficiency as we continue to scale the business."
Due to unprecedented global economic conditions and uncertainty resulting from the COVID-19 pandemic, the Company will not be providing an outlook for 2020 at this time. We are closely monitoring the global impact to the health systems where we conduct business and the slowdown in business activity related to COVID-19, and hope to provide better clarity about our outlook for 2020 on our first quarter results call. In response to the rapidly changing conditions resulting from the COVID-19 pandemic, we have taken steps to limit business activities, to limit spending and maintain only key business functions in order to continue to fulfill product orders and support our customers while also taking proactive measures to protect the health and safety of our employees and their families consistent with local guidelines.
U.S. ESS product sales increased 33% to $4.4 million in the fourth quarter of 2019 and 36% to $14.9 million in the full year of 2019. Outside the U.S. ("OUS") ESS product sales decreased 15% (13% in constant currency) to $3.0 million for the fourth quarter of 2019 due primarily to the timing of distributor orders, while increasing 8% (13% in constant currency) to $13.4 million in the full year of 2019. Worldwide, ESS product sales increased 8% (9% in constant currency) and 21% (23% in constant currency) for the fourth quarter and full year of 2019, respectively.
U.S. IGB sales increased 23% to $1.2 million for the fourth quarter of 2019 and decreased 4% to $5.2 million for the full year of 2019. OUS IGB product sales increased 7% (9% in constant currency) to $3.1 million and decreased 5% (2% in constant currency) to $11.7 million for the fourth quarter and full year of 2019, respectively. Our efforts to expand IGB therapy in the U.S. market and advance twelve-month therapy OUS improved in the fourth quarter leading to reported growth in both regions and lifting our full year results close to break even with the prior year. Worldwide, IGB sales increased 11% (13% in constant currency) and decreased 5% (3% in constant currency) for the fourth quarter and full year of 2019, respectively.
Worldwide Endoscopy product sales increased 9% (10% in constant currency) and 10% (12% in constant currency) for the fourth quarter and full year of 2019, respectively. ESS product sales represented 64% and 63% of total Endoscopy sales for the fourth quarter and full year of 2019, respectively. In the U.S., Endoscopy sales increased 31% to $5.6 million and 22% to $20.1 million for the fourth quarter and full year of 2019, respectively.
The divestiture of our Surgical products in December of 2018 reduced total revenues by $4.1 million and $13.7 million for the fourth quarter and full year of 2019, respectively. We divested the Surgical products line in order to strengthen Apollo’s focus on our Endoscopy products, which we believe have high growth potential.
Gross margin for the fourth quarter of 2019 was 49%, compared to 47% for the fourth quarter of 2018. Gross margin for the full year of 2019 decreased to 51% compared to 55% for the full year of 2018 as a result of a greater proportion of our overall product sales coming from our ESS products, which realize a lower gross margin than our other products. Management has previously discussed its ongoing gross margin improvement initiative.

Total operating expenses decreased $11.2 million to $12.7 million for the fourth quarter of 2019 and decreased $24.1 million to $49.2 million for the full year of 2019 compared to the same periods of 2018. Excluding the one-time $7.8 million loss on divestiture of our Surgical products in December of 2018, the subsequent reduction in intangible asset amortization expense of $1.2 million and $5.0 million for the fourth quarter and full year of 2019, respectively resulting from this divestiture and a one-time $5.6 million settlement gain reported in the first quarter of 2019, total operating expenses decreased $2.3 million and $5.7 million for the fourth quarter and full year of 2019, respectively. This reduction in recurring operating expenses was the result of lower U.S. direct to consumer advertising and lower clinical trial costs as enrollment or other milestones were reached on the clinical studies that the Company is funding.
Net loss for the fourth quarter of 2019 was $7.2 million compared to $18.4 million for the fourth quarter 2018. For the full year, net loss was $27.4 million in 2019 compared to $45.8 million in 2018.
Cash, cash equivalents and restricted cash were $30.9 million as of December 31, 2019.
Conference Call
Apollo will host a conference call on March 26, 2020 at 3:30 p.m. Central Time / 4:30 p.m. Eastern Time to discuss Apollo’s operating results for the fourth quarter and year ended December 31, 2019.
To participate in the conference call dial 844-369-8770 for domestic callers and +1-862-298-0840 for international callers. A live webcast of the conference call will be made available on the "Events and Presentations" section of our Investor Relations website: ir.apolloendo.com.
A replay of the webcast will remain available on Apollo’s website, www.apolloendo.com, following the call.
Non-GAAP Financial Measures
To supplement our financial results, we are providing a non-GAAP financial measure, percentage revenue change in constant currency, which removes the impact of changes in foreign currency exchange rates that affect the comparability and trend of revenues compared to the same period of the prior year. Percentage revenue change in constant currency is calculated by translating current foreign currency sales at last year’s exchange rate. This supplemental measure of our performance is not required by, and is not determined in accordance with GAAP.
We believe the non-GAAP financial measure included herein is helpful in understanding our current financial performance. We use this supplemental non-GAAP financial measure internally to understand, manage and evaluate our business, and make operating decisions. We believe that making non-GAAP financial information available to investors, in addition to GAAP financial information, may facilitate more consistent comparisons between the company’s performance over time with the performance of other companies in the medical device industry, which may use similar financial measures to supplement their GAAP financial information. However, our non-GAAP financial measure is not meant to be considered in isolation or as a substitute for the comparable GAAP metric.

On March 26, 2020 Scholar Rock (NASDAQ: SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported the publication in the peer-reviewed journal Science Translational Medicine of preclinical data that established the therapeutic rationale for evaluating a potent and highly selective inhibitor of transforming growth factor-beta 1 (TGFβ1) activation to overcome primary resistance to checkpoint inhibitor therapy (Press release, Scholar Rock, MAR 26, 2020, View Source [SID1234555882]).

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"With this publication, we are sharing the strong body of preclinical evidence we have built supporting the clinically-derived rationale for evaluating TGFβ1’s key role in primary resistance to checkpoint inhibitor therapy and the potential of a highly specific inhibitor of TGFβ1 activation to overcome this challenge. In the second half of this year, we may gain early insights from our Phase 1 proof-of-concept trial in patients with solid tumors on SRK-181’s potential to overcome the immune exclusion that we believe leads to primary resistance to anti-PD-(L)1 therapy," said Alan Buckler, Ph.D., Chief Scientific Officer of Scholar Rock. "Moreover, these published data provide further validation of Scholar Rock’s proprietary platform to develop antibodies that locally and selectively target the precursor form of growth factors with the aim of avoiding the dose-limiting toxicities that have hindered traditional approaches to targeting growth factors."

The introduction of immunotherapy, including checkpoint inhibitor therapy, has revolutionized the treatment of a wide variety of cancers, delivering profound and durable responses for many patients. Unfortunately, this therapeutic approach is only effective in a small subset of patients; even at the outset of treatment, some tumors show primary resistance to anti-PD-(L)1. Human tumor profiling and several preclinical studies have implicated TGFβ signaling activity as a potential point of intervention to overcome primary resistance to checkpoint inhibition. However, the development of therapies targeting TGFβ signaling has been hindered by dose-limiting cardiotoxicities, potentially due to non-selective inhibition of multiple TGFβ isoforms.

As detailed in the Science Translational Medicine publication "Selective inhibition of TGFβ1 activation overcomes primary resistance to checkpoint blockade therapy by altering tumor immune landscape," SRK-181 inhibits TGFβ1 activation with high selectivity and has demonstrated in preclinical studies the potential to overcome primary resistance and meaningfully expand the number of patients who could benefit from checkpoint inhibitor therapy. (Martin et al., Sci. Transl. Med. 12: 25 March 2020)

Based on RNAseq data from the Cancer Genome Atlas (TCGA), TGFβ1 is the most prevalent isoform expressed in the majority of human cancer types, with the exception of breast cancer, mesothelioma, and prostate cancer, where TGFβ3 is also expressed. This finding was also observed in examination of individual samples.
TGFβ1 is likely expressed by multiple cell types within the tumor microenvironment and each cell type produces TGFβ1 in different large latent complexes (LLCs). This is supported by TCGA data, which indicates essentially all tumor types express mRNA encoding all four LLC-presenting molecules, namely LTBP1, LTBP3, GARP, and LRRC33. By targeting the precursor form of TGFβ1, SRK-181 achieves exquisite isoform specificity, inhibiting latent TGFβ1 activation in all known molecular contexts without binding to latent TGFβ2, latent TGFβ3, or any of the three active TGFβ growth factors.
Scholar Rock identified three syngeneic mouse tumor models that recapitulate key features of human primary resistance to checkpoint inhibitor therapy: MBT-2 (bladder cancer), Cloudman S91 (melanoma) and the EMT-6 (breast cancer) mouse models. Combination treatment with SRK-181-mIgG1 and an anti-PD-1 therapy resulted in tumor regression or control and survival benefit across these three identified cancer models. This tumor response was also shown to be durable, where mice with no measurable tumor at treatment cessation remained tumor free.

MBT-2 bladder
cancer model
(Response**: %, N)

Cloudman S91
melanoma model
(Response***: %, N)

EMT-6 breast
cancer model
(Response*: %, N)

Control

0% (0/12)

0% (0/11)

0% (0/9)

Anti-PD1 monotherapy

0% (0/13)

25% (3/12)

0% (0/9)

SRK-181-mIgG1 monotherapy

0% (0/12)

0% (0/12)

0% (0/10)

Anti-PD-1/SRK-181-mIgG1, 3 mg/kg

29% (4/14)

75% (9/12)

NT

Anti-PD-1/SRK-181-mIgG1, 10 mg/kg

57% (8/14)

44% (4/9)

50% (5/10)

Anti-PD-1/SRK-181-mIgG1, 30 mg/kg

NT

73% (8/11)

NT

* For EMT-6: Response is defined as animals that achieved a tumor volume at study end of less than 25% of the 2,000mm3 survival threshold.
** For MBT-2: Response is defined as animals that achieved a tumor volume at study end of less than 25% of the 1,200mm3 survival threshold.
*** For Cloudman S91: Response is defined as animals that achieved a tumor volume at study end of less than 25% of the 2,000mm3 survival threshold.
NT: Not tested

The tumor regression and control demonstrated in the EMT-6 breast cancer model, which expresses both TGFβ1 and TGFβ3, suggest TGFβ1 is the key isoform contributing to checkpoint resistance and highlights the possibility that selective TGFβ1 inhibition may have therapeutic potential in overcoming primary resistance across a broad spectrum of cancers, irrespective of the expression of other TGFβ isoforms.
Dose-limiting cardiotoxicities have challenged the therapeutic development of TGFβ pathway inhibitors. Selective inhibition of latent TGFβ1 activation with SRK-181 has demonstrated an improved safety profile as compared to pan-TGFβ inhibitors. In a 4-week repeat-dose rat toxicology study, the no-observed-adverse-effect-level (NOAEL) was the highest dose tested of 100 mg/kg once weekly, which is well above the doses necessary to elicit robust anti-tumor responses when combined with anti-PD-1 antibody.
Following combination treatment with SRK-181-mIgG1 and anti-PD-1, there were significant increases in intratumoral effector T cells and decreases in immunosuppressive myeloid cells, suggesting TGFβ1’s multiple contributions to primary resistance to checkpoint inhibition.
Overall percentage of the CD45+ immune compartment did not change.
Ten-fold increase in CD8 T cell representation (average of 34% vs. control average of 3.5%). Single-agent treatment with anti-PD-1 or SRK-181-mIgG1 only resulted in modest increases that did not reach significance in the study.
Significant reduction in immunosuppressive M2-like macrophages (14% vs. control average of 47%) and myeloid-derived suppressor cells (MDSC; 1.4% vs. control average of 10.9%).
About SRK-181

SRK-181 is a potent and highly selective inhibitor of TGFβ1 activation and is an investigational product candidate being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies. TGFβ1 is the predominant TGFβ isoform expressed in many human tumors, particularly for those tumors where checkpoint therapies are currently approved. Based on analyses of human tumors that are resistant to anti-PD-(L)1 therapy, TGFβ1 is implicated as a key contributor to exclude immune cell entry into the tumor microenvironment, thereby preventing normal immune function. By overcoming this immune cell exclusion, Scholar Rock believes SRK-181 has the potential to induce tumor regression when administered in combination with anti-PD-(L)1 therapy. A Phase 1 proof-of-concept clinical trial in patients with locally advanced or metastatic solid tumors is ongoing. The effectiveness and safety of SRK-181 have not been established and SRK-181 has not been approved for any use by the FDA or any other regulatory agency.