On August 3, 2022 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported financial results for the second quarter ended June 30, 2022 and provided a review of recent business and clinical highlights (Press release, Xencor, AUG 3, 2022, View Source [SID1234617397]).

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!

"Xencor is applying our leading protein engineering tools and proprietary XmAb technologies to create a broad portfolio of novel bispecific antibodies and cytokines, and we are using our resources on multiple clinical programs where the data to date indicate we have the greatest potential for success," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "We are expanding and maturing our clinical portfolio of XmAb drug candidates, recently dosing the first patient in a Phase 1 study of XmAb819, our ENPP3 x CD3 bispecific antibody for renal cell carcinoma, which is engineered with our multivalent 2+1 antibody format, as well as the first patient in our second Phase 2 study of vudalimab, our PD-1 x CTLA-4 bispecific antibody, in certain gynecologic tumors and clinically defined high-risk mCRPC."

"Later this year, we plan to present additional clinical data from our vudalimab and plamotamab programs and initial data from our IL2-Fc autoimmune program, XmAb564, in healthy volunteers. Near year-end we also expect to dose the first patient in the Phase 1 study of XmAb808, our B7-H3 x CD28 bispecific antibody, placing Xencor at the forefront of efforts to engage CD28 to selectively activate T cells."

Recent Portfolio Highlights

Vudalimab (PD-1 x CTLA-4): The first patient was dosed in a Phase 2 study evaluating vudalimab monotherapy in patients with clinically-defined high-risk metastatic castration-resistant prostate cancer (mCRPC) and certain gynecologic malignancies. A separate, ongoing Phase 2 study, in which vudalimab is being evaluated in combination with chemotherapy or a PARP inhibitor depending on the tumor’s molecular subtype, is enrolling patients, and the Company plans to present early data from the study later this year.
XmAb104 (PD-1 x ICOS): Initial dose-escalation data from the Phase 1 study in patients with advanced solid tumors were presented in a poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2022. XmAb104 was well tolerated and exhibited a distinct safety profile compared to other clinical-stage ICOS programs. Anti-tumor activity and biomarker activity consistent with T-cell engagement were observed. The expansion portion of the study is exploring XmAb104 in combination with ipilimumab in parallel cohorts of patients with several advanced solid tumor types.
XmAb819 (ENPP3 x CD3): The first patient was dosed in a Phase 1 study in patients with advanced renal cell carcinoma. XmAb819 uses the XmAb 2+1 bispecific antibody format for greater selectivity for ENPP3-expressing tumor cells compared to normal cells, which express lower levels of ENPP3.
XmAb808 (B7-H3 x CD28): The company is initiating a Phase 1 study in combination with pembrolizumab. CD28 is a key immune co-stimulatory receptor on T cells; however, the ligands that activate T cells through CD28 are usually not expressed on tumor cells. Targeted CD28 bispecific antibodies are a new class of bispecific, engineered to provide conditional co-stimulation of T cells when the molecule is also bound to tumor cells, which may enhance the activity CD3 bispecifics and checkpoint inhibitors. XmAb808 targets the broadly expressed tumor antigen B7-H3.
Progress Across Partnerships

Vir Biotechnology, Inc.: In the second quarter of 2022, Xencor recognized $22.1 million in royalty revenue under the Company’s agreement with Vir. Sotrovimab, an antibody that targets the SARS-CoV-2 virus and incorporates Xencor’s Xtend Fc domain for longer duration of action, has been made available by Vir and its partner Glaxo Wellcome UK Limited and GlaxoSmithKline Biologicals S.A. Sotrovimab’s authorization was previously ended in all U.S. regions.
Alexion Pharmaceuticals, Inc.: In July 2022, Ultomiris (ravulizumab-cwvz), which incorporates an Xtend Fc domain, received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in Europe for patients with generalized myasthenia gravis. In the second quarter of 2022, Xencor earned $6.7 million from Alexion on net sales of Ultomiris. Ultomiris is a registered trademark of Alexion Pharmaceuticals, Inc.
Caris Life Sciences: In August 2022, the Company announced a new target discovery option and license agreement to create XmAb bispecific or multi-specific antibodies with Caris’ unique human tissue bank and bioinformatics approach to find addressable tumor markers.
Financial Results for the Second Quarter Ended June 30, 2022

Cash, cash equivalents, receivables and marketable debt securities totaled $679.7 million as of June 30, 2022, compared to $664.1 million on December 31, 2021. During the first half of 2022, the Company received royalty and milestone payments from partners of $113.7 million, which offset net spending on operations of $105.0 million and resulted in an increase in cash balance amounts at June 30 relative to the 2021 year-end amount.

Total revenue for the second quarter ended June 30, 2022 was $30.2 million, compared to $67.4 million for the same period in 2021. Revenues earned in the second quarter of 2022 were primarily royalties from the Alexion and Vir agreements, compared to the same period in 2021, which were primarily from the Janssen and Novartis collaborations, and royalty revenue from Alexion. Revenues for the six months ended June 30, 2022 were $115.7 million, compared to $101.4 million for the same period in 2021. Revenues for the six-month period in 2022 were primarily from milestone revenue from Astellas and royalty revenue from Alexion and Vir, compared to the same period in 2021, which were earned primarily from the collaborations with Janssen and Novartis, milestone revenue from MorphoSys and the royalties from Alexion and Vir.

Research and development (R&D) expenses for the second quarter ended June 30, 2022 were $47.1 million, compared to $49.5 million for the same period in 2021. Decreased R&D spending for second quarter of 2022 compared to 2021 reflects decreased spending on plamotamab and XmAb819 (ENPP3 x CD3) programs, partially offset by increased spending on our new development programs, XmAb808 (B7-H3 x CD28) and XmAb662 (IL12-Fc). R&D expenses for the six months ended June 30, 2022 were $94.8 million, compared to $90.9 million for the same period in 2021. Increased R&D spending for the first six months of 2022 compared to 2021 is primarily due to an increase in stock-based compensation charges.

General and administrative (G&A) expenses for the second quarter ended June 30, 2022 were $11.1 million, compared to $8.9 million for the same period in 2021. G&A expenses for the six months ended June 30, 2022 were $22.4 million, compared to $17.1 million for the same period of 2021. Increased G&A spending for the second quarter and first six months of 2022 compared to amounts for the same periods in 2021 reflects increased spending on professional services and additional facility costs.

Other expenses for the second quarter ended June 30, 2022 were $6.0 million, compared to other income of $43.2 million in the same period in 2021. Other expenses for the six months ended June 30, 2022 were $8.8 million, compared to other income of $56.3 million in the same period in 2021. Other expenses for the second quarter and first six months of 2022 include unrealized losses on the Company’s marketable equity investments while other income for the second quarter and first six months of 2021 includes realized gains on the sale of an investment equity security and an increase in unrealized gains on the Company’s marketable equity investments.

Non-cash, stock-based compensation expense for the six months ended June 30, 2022 was $23.4 million, compared to $17.6 million for the same period in 2021.

Net loss for the second quarter ended June 30, 2022 was $34.0 million, or $(0.57) on a fully diluted per share basis, compared to net income of $52.2 million, or $0.87 on a fully diluted per share basis, for the same period in 2021. For the six months ended June 30, 2021, net loss was $10.4 million, or $(0.17) on a fully diluted per share basis, compared to net income of $49.8 million, or $0.82 on a fully diluted per share basis, for the same period in 2021. Net loss reported for the second quarter ended June 30, 2022 and first six months of 2022, compared to the net income reported for the same periods in 2021, were primarily due to realized gain on an equity investment and an increase in unrealized gains on marketable equity securities during the second quarter and six months ended June 30, 2021.

The total shares outstanding were 59,684,420 as of June 30, 2022, compared to 58,315,485 as of June 30, 2021.

Financial Guidance

Based on current operating plans, Xencor expects to have cash to fund research and development programs and operations through the end of 2025. The Company expects to end 2022 with between $550 million and $575 million in cash, cash equivalents, receivables and marketable debt securities.

Conference Call and Webcast

Xencor will host a conference call today at 4:30 p.m. ET (1:30 p.m. PT) to discuss the second quarter 2022 financial results and provide a corporate update. To participate in the conference call,

The live webcast will be available under "Events & Presentations" in the Investors section of the Company’s website at investors.xencor.com and will be archived for at least 30 days. Conference call participants may register through the following link: register.vevent.com/register/BI8b3886bf9772414c8dd5900d3aa4457b.

On August 3, 2022 TransCode Therapeutics, Inc. (Nasdaq: RNAZ) ("TransCode" or the "Company"), the RNA oncology company, and The University of Texas MD Anderson Cancer Center ("MD Anderson"), reported a strategic alliance to advance TransCode’s pipeline of RNA-targeted oncology therapeutic and diagnostic candidates (Press release, TransCode Therapeutics, AUG 3, 2022, View Source [SID1234617396]).

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!

Through the alliance, TransCode and MD Anderson scientists will collaborate on preclinical studies to further validate TransCode’s therapeutic and diagnostic candidates and to expand the reach of TransCode’s discovery engine. The results of these studies will inform future clinical trials with these agents, including trials to be led at MD Anderson.

"RNA-based therapeutics offer exciting possibilities to treat cancer. We can now examine how regulatory RNAs affect signaling, both spatially and temporally, at the single-cell level in tumor cells, immune cells and stem cells — all critical for tumor progression, relapse and immune evasion," said principal investigator Sendurai Mani, Ph.D., Professor of Translational Molecular Pathology. "Our goals in collaborating with TransCode are to gain a deeper understanding of RNA-targeted therapies and to bring innovative new treatment options to our patients."

The collaboration has the potential to inform multiple clinical programs in TransCode’s pipeline, starting with its lead therapeutic candidate, TTX-MC138, designed to treat multiple metastatic cancers. Future clinical trials will be designed and led by Vivek Subbiah, M.D., Associate Professor of Investigational Cancer Therapeutics at MD Anderson.

"This strategic alliance offers the opportunity to further unlock the potential of our therapeutic pipeline by combining the promise of our image capable delivery platform and discovery engine with the unique talent and resources found at MD Anderson," said Zdravka Medarova, PhD, Co-Founder and CTO of TransCode.

Prior to a Phase I clinical trial, TTX-MC138 is scheduled to enter a first-in-human Phase 0 clinical trial designed to demonstrate delivery of the therapeutic candidate to metastatic lesions in patients with advanced solid tumors.

"We are acutely aware of the expectations that come with a therapeutic approach that has the potential to induce durable regressions of metastatic disease. We are committed to taking every opportunity to fulfill the promise of RNA in cancer," said Michael Dudley, Co-Founder and CEO of TransCode.

On August 3, 2022 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported financial results and business highlights for the second quarter of 2022 as well as upcoming anticipated corporate milestones (Press release, Surface Oncology, AUG 3, 2022, View Source [SID1234617395]).

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 the second quarter, we presented encouraging new SRF388 clinical data in an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting," said Rob Ross, M.D., chief executive officer. "SRF388, our first-in-class anti-IL27 antibody, demonstrated activity as both a monotherapy and in combination with other IO agents, bolstering our belief that this agent holds the potential to treat a broad range of tumor types. With cash runway into 2024, we believe we are well positioned to deliver a series of meaningful clinical data updates across our pipeline beginning later this year and through the first half of 2023."

Second Quarter and Subsequent Corporate Highlights

In June, Surface announced the publication of a new study highlighting the role of the IL-27 pathway in hepatocellular carcinoma (HCC). Surface collaborated with Cedars-Sinai Medical Center and Fox Chase Cancer Center to conduct the study which evaluated the role of the IL-27 pathway in the development of HCC. The study was published in the online edition of Cancer Discovery, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

In June, Surface presented new SRF388 Phase 1/1b clinical data at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting. SRF388 demonstrated clinical activity in multiple solid tumor types with three partial responses across non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC) and HCC. Surface also announced plans to conduct a new expansion study of SRF388 in combination with pembrolizumab in up to 40 patients with relapsed/refractory NSCLC.

In June, Surface announced the appointment of Carsten Brunn, Ph.D., to the board of directors. Dr. Brunn brings more than 25 years of senior leadership experience within multiple biotech and pharmaceutical companies worldwide.

In April, Surface announced the initiation of two Phase 2 clinical studies evaluating SRF388 in multiple tumor types, including a randomized Phase 2 clinical study evaluating SRF388 in combination with atezolizumab and bevacizumab in patients with treatment-naïve HCC and a Phase 2 monotherapy study in patients with previously-treated NSCLC. In addition, the company announced an expansion of the open-label lead-in of the SRF388 randomized Phase 2 study in first-line HCC. The 30-patient lead-in is expected to inform the start of the randomized stage and could elucidate important biomarkers to support enriched patient selection.

At the AACR (Free AACR Whitepaper) Annual Meeting 2022 in April, Surface presented preclinical and translational data supporting the SRF388 recommended Phase 2 monotherapy dose of 10 mg/kg administered intravenously every four weeks.

In April, the company announced that it was recognized by the Boston Business Journal as one of the Best Places to Work for the second year in a row

In Q2, Surface received the anticipated $30 million milestone payment from GlaxoSmithKline for the initiation of the first Phase 1 study for GSK4381562. As part of the licensing agreement, Surface is eligible to receive up to $700 million in potential milestone payments, as well as tiered royalties on global net sales.

The company granted non-qualified stock options to one new employee to purchase 80,000 shares of the company’s common stock with a per share exercise price of $1.64, the closing price on August 1, 2022. The option grant was made under Surface’s 2021 Inducement Plan (the Plan) as an inducement material to the employee entering into employment with the company in accordance with Nasdaq Listing Rule 5635(c)(4) and was granted pursuant to the terms of the Plan.
Selected Anticipated Near-term Corporate Milestones

The company expects to provide a clinical data update on SRF617, a fully human antibody designed to inhibit CD39, in the fourth quarter of 2022.

Surface remains on track to file an Investigational New Drug (IND) application for SRF114, a fully human IgG1 anti-CCR8 antibody, before the end of the year.

Surface anticipates providing multiple SRF388 clinical updates in the first half of 2023, including initial safety and efficacy data from the expanded 30 patient lead-in to the Phase 2 study in first-line HCC.
Financial Results
As of June 30, 2022, cash, cash equivalents and marketable securities were $156.6 million, compared to $154.1 million on December 31, 2021.

General and administrative (G&A) expenses were $6.4 million for both the second quarter ended June 30, 2022, and for the same period in 2021. Decreases in legal and professional fees were partially offset by increased personnel related costs and increased insurance premiums. G&A expenses included $1.3 million in stock-based compensation expense for the second quarter ended June 30, 2022.

Research and development (R&D) expenses were $18.2 million for the second quarter ended June 30, 2022, compared to $12.7 million for the same period in 2021. This increase was primarily driven by progress on our SRF617 and SRF388 Phase 1 and Phase 2 clinical trials. R&D expenses included $0.8 million in stock-based compensation expense for the second quarter ended June 30, 2022.

For the second quarter ended June 30, 2022, net loss was $25.2 million, or basic and diluted net loss per share of $0.46. Net loss was $19.0 million for the same period in 2021, or basic and diluted net loss per share of $0.44.

Surface Oncology continues to project that current cash and cash equivalents are sufficient to fund the company into 2024.

On August 3, 2022 Signify Health, Inc. (NYSE: SGFY), a leading healthcare platform that leverages advanced analytics, technology and nationwide healthcare networks to create and power value-based payment programs, reported the Company’s financial results for the second quarter 2022 (Press release, Signify Health, AUG 3, 2022, View Source [SID1234617394]).

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!

"Our strong second quarter results reflect the meaningful value we are delivering for our clients and the members we serve through our unique capabilities in closing hard-to-reach gaps in care, engaging people in their homes, and connecting providers with the actionable insights required to be successful in value-based payment models," said Kyle Armbrester, Chief Executive Officer of Signify Health. "We are seeing tremendous demand for our comprehensive evaluations as our health plan clients prioritize member engagement and closing clinical, behavioral, and social care gaps in order to improve health outcomes. In order to meet the needs of our clients, we are focused on driving operational efficiency, expanding our ability to bring connected diagnostic devices into the home, and returning people to care by connecting them with primary care providers, specialists, and care management programs."

Mr. Armbrester continued, "Since our acquisition of Caravan Health in March, our total cost of care enablement business has outperformed our expectations, including strong shared savings performance and adding new clients that are expected to significantly expand the population managed through our platform in 2023. We are also seeing increasing interest from healthcare providers in moving forward with their roadmaps for beginning, or expanding, their participation in total cost of care payment programs in partnership with us, including several clients who quickly transitioned from episodes-focused models to total cost of care programs. We believe this is a clear testament to the value and deep relationships Signify has created with our health system partners, and their confidence in our ability to drive savings for the healthcare system. Overall, Signify has significant momentum heading into the second half of the year as we continue to pursue our mission to accelerate the transformation of the U.S. healthcare system from fee-for-service to value-based care."

Second Quarter 2022 Financial Results

Total revenue for the second quarter grew 16% to $246.2 million, up from $212.8 million in the year-ago period. Growth in the second quarter of 2022 was driven by an 18% increase in Home & Community Services (HCS) segment revenue to $207.6 million and a 3% increase in Episodes of Care Services (ECS) segment revenue to $38.6 million.
HCS revenue was a quarterly record and is attributable to an increase in in-home evaluation (IHE) volume, which grew to approximately 624 thousand in the second quarter from approximately 497 thousand in the year-ago period.
Caravan Health, which was acquired in March 2022, contributed $16.6 million of revenue to the ECS segment in the second quarter.
Second quarter net loss was $490.0 million compared to a net loss of $0.1 million for the year-ago period. Second quarter net loss included a $519.9 million loss on impairment related to the wind down of the ECS segment and $26.9 million of other income related to the remeasurement of the fair value of our Equity Appreciation Rights (EAR) due to a decrease in the Company’s stock price in the second quarter.
Non-GAAP Adjusted EBITDA1 for the second quarter increased 15% to $62.6 million, compared to $54.6 million for the second quarter 2021, driven primarily by HCS revenue growth.
2022 Outlook

The Company is providing full year 2022 estimates as follows:

HCS revenue in the range of $800 million to $810 million;
Caravan Health revenue in the range of $45 million to $48 million for the 10-month period following the acquisition;
Adjusted EBITDA margin for HCS and Caravan Health of 29% to 30%, which is before shared costs that are currently allocated to the company’s ECS segment;
Of the $60 million in annualized shared costs that are currently allocated to the ECS segment, the Company continues to expect to eliminate approximately $30 million to $35 million in annualized expenses by the end of 2022
The Company is not providing guidance for the Episodes business that it is in the process of winding down.
1Adjusted EBITDA and Adjusted EBITDA margin are non-GAAP financial measures. Refer to the reconciliation in "Non-GAAP Financial Measures." We have not reconciled 2022 guidance for adjusted EBITDA to net income (loss), the most directly comparable GAAP measure, and have not provided forward-looking guidance for net income (loss) because of the uncertainty around certain items that may impact net income (loss), including, among others, the wind down of the Episodes of Care Services business, asset impairments, stock-based compensation and the fair valuation of the EARs, that are not within our control or cannot be reasonably estimated.

Conference Call Information

Signify Health will host a conference call to discuss the Company’s second quarter 2022 results on August 4, 2022 at 8:30am ET. A live audio webcast of the conference call may be accessed through the investor relations section of Signify Health’s website at View Source and will be available for replay for one year.

On August 3, 2022 Seres Therapeutics, Inc. (Nasdaq: MCRB), a leading microbiome therapeutics company, reported second quarter 2022 financial results and provided business updates (Press release, Seres Therapeutics, AUG 3, 2022, View Source [SID1234617393]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We made considerable progress on key clinical, corporate and commercial initiatives that bolster our leadership in the microbiome field," said Eric Shaff, President and Chief Executive Officer at Seres. "We were delighted to report positive confirmatory safety and efficacy data from our SER-109 ECOSPOR IV study in recurrent C. difficile infection, which help complete the FDA’s predefined safety database requirements for investigational product SER-109. These ECOSPOR IV data are consistent with our prior ECOSPOR III study and we expect them to complete the SER-109 Phase 3 development program. These data form the basis for our recently initiated rolling BLA submission, which we expect to complete in the coming weeks. In addition, we continue to advance our commercial readiness activities with our collaborator, Aimmune Therapeutics, Inc., a Nestlé Health Science company, in advance of our expected launch in the first half of 2023. We also recently strengthened our balance sheet with a $100 million registered direct equity offering to further support our efforts to prepare for a successful SER-109 product launch."

Program and Corporate Updates

SER-109 Phase 3 ECOSPOR III study in recurrent C. difficile infection: SER-109, an investigational oral, live microbiome therapeutic, achieved its primary endpoint of superiority to placebo in reducing recurrence in patients with recurrent CDI (rCDI).

In June 2022, Seres reported positive confirmatory results from ECOSPOR IV, an open-label study of SER-109 in patients with rCDI (ClinicalTrials.gov identifier: NCT03183141) designed to expand the SER-109 safety database in support of the ongoing rolling BLA filing. The open-label ECOSPOR IV study evaluated adults with rCDI, providing 24-week data for an additional 263 subjects administered SER-109. In the study, 91.3% of patients in the overall population achieved a sustained clinical response at eight weeks. The results were consistent with the previous ECOSPOR III results and were consistent across key subpopulations, including in individuals with a first recurrence of CDI.

The study enrolled subjects with a clinical profile consistent with those commonly evaluated and treated in clinical practice. The overall safety profile through the 24-week follow-up showed that SER-109 was well tolerated, consistent with the safety profile observed in ECOSPOR III. Similarly low recurrence rates were observed in key subpopulations at eight weeks, including subjects with a first recurrence (6.5%), second recurrence (6.1%) and three or more recurrences (13.8%). Furthermore, the study allowed for initial CDI diagnosis to be made with either toxin or PCR, reflecting the variability across local medical practices; on-study recurrences continued to be confirmed by toxin to ensure study data integrity.

The ECOSPOR IV data were consistent with the prior Phase 3 ECOSPOR III study evaluating SER-109 for the treatment of rCDI. These results, published in the New England Journal of Medicine (NEJM) indicated that SER-109 was superior to placebo in reducing CDI recurrence, with 88% of SER-109 patients achieving a sustained clinical response compared to 60% on placebo at eight weeks. SER-109 was well tolerated in the study, with no drug-related serious adverse events.

The Company recently initiated a rolling BLA submission for SER-109 and expects to complete the filing in the coming weeks.

Seres has an active SER-109 expanded access program at various sites across the U.S. The program is designed to enable eligible adults with rCDI to obtain access to the investigational therapeutic prior to a potential FDA product approval.

The Company continues to prepare for a successful product launch with Aimmune Therapeutics, Inc. The Company believes that a substantial commercial opportunity exists for SER-109. The cost of a patient with CDI has been estimated to result in approximately $34,000 in annual direct healthcare expenses; this does not include the substantial indirect costs associated with this disease. There are approximately 170,000 cases of rCDI annually in the U.S. and CDI results in over 20,000 deaths annually.

Seres continues to execute pre-commercialization activities in collaboration with Aimmune Therapeutics, including market education and data dissemination to the medical community. In addition, activities are ongoing to engage payers in accordance with FDA guidance on pre-approval information exchange. The Company continues to make progress expanding commercial-scale production of SER-109 to prepare for anticipated market demand. An ongoing agreement with Bacthera, a global leader in biopharmaceutical product manufacturing, is designed to increase longer-term SER-109 product supply and adds to existing manufacturing capabilities.

SER-155 Phase 1b clinical study activities: Seres continues to advance a Phase 1b clinical study of SER-155 designed to evaluate safety and microbiome drug pharmacology. The trial will also assess the impact on infections and/or graft versus host disease, or GvHD, associated with SER-155 in adult subjects who are undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). SER-155 is an investigational oral, rationally designed, cultivated microbiome therapeutic designed to reduce the incidence of gastrointestinal (GI) infections, bloodstream infections, and GvHD in patients receiving allo-HSCT. In April 2022, the SER-155 Data and Safety Monitoring Committee met as part of a planned data review and approved a recommendation to continue with enrollment in Cohort 1 based on an evaluation of available safety data. The study is being conducted at a number of leading cancer centers across the US.

SER-155 is a consortium of bacterial species selected using Seres’ reverse translation discovery and development platforms. The design incorporates microbiome biomarker data from human clinical data and nonclinical human cell-based assays and in vivo disease models. The SER-155 composition aims to decrease the colonization and translocation of antibiotic-resistant bacteria in the GI tract to decrease the incidence of bloodstream infections and additionally to modulate host immune responses to decrease GvHD. In addition to SER-109, SER-155 represents Seres’ second active clinical development program in its Infection Protection franchise.

Registered direct common stock offering: In July 2022, the Company closed a registered direct equity offering of its common stock resulting in proceeds, net of placement agent fees, of approximately $96.8 million. The Company intends to use the net proceeds from the offering for commercial readiness and manufacture of SER-109 for the U.S. market, including expanding longer-term commercial manufacturing capacity, advancing the clinical development of SER-109 for the EU market, and other general corporate and working capital purposes. The offering included participation by Federated Hermes Kaufmann Funds, Flagship Pioneering, Heights Capital Management, Inc., Janus Henderson Investors, and Nestlé Health Science, as well as other new and existing investors.

2022 Digestive Disease Week (DDW) annual meeting: Seres presented a pre-planned exploratory analysis from the SER-109 ECOSPOR III trial showing that approximately two-thirds of CDI recurrences occurred within the first two weeks following antibiotic treatment for CDI – the window of vulnerability – when the microbiome is further decimated and C. difficile spores, untouched by antibiotics, are free to germinate into toxin-producing vegetative bacteria. These findings suggest that the first two weeks following antibiotic treatment may be the optimal time when microbiome therapeutics may have the greatest potential benefit, to restructure bacterial diversity and disrupt the cycle of recurrent C. difficile.

The Company also presented data from stool samples collected from ECOSPOR III participants that were analyzed for changes in their microbial makeup and fatty acid concentrations across the eight weeks following SER-109 treatment. For participants who received SER-109, butyrate, valerate and hexanoate levels rapidly increased, starting within the two-week window of vulnerability, and remained significantly higher than the placebo group for the eight-week data analysis period. Fatty acids with long and medium carbon chain lengths, such as butyrate, valerate and hexanoate, have been shown to inhibit the growth of C. difficile.

2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting: The Company presented data detailing the design of the Phase 1b trial evaluating the efficacy, safety and pharmacokinetics of SER-155 in adults undergoing allo-HSCT. In addition, Seres presented preclinical data supporting further investigation of microbiome therapeutics to prevent or treat GI mucositis – a common and often painful complication of radiation and chemotherapy involving the breakdown of the rapidly-dividing epithelial cells lining the GI tract.

Infection Protection research: The Company continues to conduct research to bring forward new clinical candidates related to using microbiome therapeutics as a novel approach for Infection Protection for medically compromised individuals, including those with cancer neutropenia, cirrhosis, or solid organ transplant. Preclinical studies are evaluating the potential to reduce the abundance of targeted pathogens to decrease the potential for pathogen transmission, strengthen epithelial barriers to further reduce the frequency of bloodstream infections and to modulate immune responses to tackle medical complications such as graft versus host disease. The Company anticipates advancing an additional Infection Protection therapeutic candidate into clinical development in 2023.

Ulcerative colitis (UC) research: The Company previously reported clinical, microbiome and metabolomic data from the SER-287 Phase 2b study and the first cohort of its SER-301 Phase 1b study. Available data for these investigational microbiome therapeutics suggest that there may be an opportunity to utilize biomarker-based patient selection and stratification for future studies. Research activities remain ongoing to inform potential further development activities.

Financial Results

Seres reported a net loss of $64.7 million for the second quarter of 2022, as compared with a net loss of $48.3 million for the same period in 2021.

Research and development expenses for the second quarter of 2022 were $43.9 million, compared with $36.0 million for the same period in 2021. The research and development expenses were primarily related to Seres’ late-stage SER-109 clinical development program and manufacturing costs, as well as personnel expenses.

General and administrative expenses for the second quarter of 2022 were $20.3 million, compared with $17.5 million for the same period in 2021. General and administrative expenses were primarily related to personnel expenses, professional fees, including SER-109 commercial readiness and pre-launch expenses, and facility costs.

Seres ended the second quarter of 2022 with approximately $195.8 million in cash, cash equivalents and investments. Subsequent to the end of the quarter, in July 2022, the Company closed a $100 million registered direct offering of its common stock, resulting in proceeds, net of placement agent and other fees, of approximately $96.8 million. As a result, the June 30, 2022, pro-forma cash balance, inclusive of the registered direct offering net proceeds, was approximately $291.4 million.

Conference Call Information

Seres’ management will host a conference call today, August 3, 2022, at 8:30 a.m. ET. To access the conference call, please dial 800-715-9871 (domestic) or 646-307-1963 (international) and reference Conference ID 3171491. To join the live webcast, please visit the "Investors and News" section of the Seres website at www.serestherapeutics.com.

A webcast replay will be available on the Seres website beginning approximately two hours after the event and will be archived for at least 21 days.