On August 8, 2022 Sesen Bio (Nasdaq: SESN) reported operating results for the second quarter ended June 30, 2022 (Press release, Sesen Bio, AUG 8, 2022, View Source [SID1234617809]). During the quarter, the Company paused clinical development of its lead asset, Vicineum for the treatment of non-muscle invasive bladder cancer (NMIBC), and turned its primary focus to the assessment of potential strategic alternatives with the goal of maximizing shareholder value, which it believes will be complete by the end of 2022 .

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Business Updates

On July 11, 2022, Sesen Bio participated in a Type B Meeting with the US Food and Drug Administration (FDA). During the meeting, the Company and the FDA discussed outstanding items related to the Company’s proposed protocol and statistical analysis plan design elements for an additional Phase 3 clinical trial for Vicineum for the treatment of NMIBC, which the Company had been evaluating for potential resubmission of a Biologics License Application for Vicineum.

On July 15, 2022, the Company executed an asset purchase agreement (the "Roche Asset Purchase Agreement") with Roche for legacy Interleukin-6 (IL-6) antagonist antibody technology owned by Sesen Bio. Pursuant to the Roche Asset Purchase Agreement, Roche purchased all patent rights and know-how related to the monoclonal antibody EBI-031 and all other IL-6 antagonist monoclonal antibody technology owned by Sesen Bio for up to $70 million. This includes a $40 million payment made by Roche to the Company upon execution of the Roche Asset Purchase Agreement, and an additional $30 million payable to Sesen Bio upon Roche’s initiation of a Phase 3 clinical trial with EBI-031 for a defined indication if initiated prior to December 31, 2026.

As a result of the Roche Asset Purchase Agreement, the Company’s previous license agreement with Roche dated June 10, 2016 (the "Roche License Agreement") was terminated. Prior to the termination of the Roche License Agreement, the Company had received $50 million in upfront and milestone payments from Roche.

On July 18, 2022, Sesen Bio announced that it had made the strategic decision to voluntarily pause further development of Vicineum in the US. The decision was based on a thorough reassessment of Vicineum following recent discussions with the FDA, which included feedback that had implications on the size, timeline, and costs of the required additional Phase 3 clinical trial for the treatment of NMIBC. The Company continues to believe that Vicineum has benefits for patients and healthcare providers that can be maximized through a company with a larger infrastructure, and as such, intends to seek a partner that can execute further development to realize the full potential of Vicineum.

As a result of this decision, the Company has turned its primary focus to the careful assessment of strategic alternatives with the goal of maximizing shareholder value. As previously disclosed, the Company is actively working with an investment bank in the assessment process, and believes it will be complete by the end of 2022.

On July 20, 2022, Sesen Bio announced the approval of a restructuring plan to reduce operating expenses and to better align its workforce with the needs of its business following the decision to pause further development of Vicineum in the US. Execution of the restructuring plan is expected to be substantially complete by the end of the fourth quarter of 2022.
Second Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $161.2 million as of June 30, 2022, compared to $151.1 million as of June 30, 2021.
R&D Expenses: Research and development expenses for the second quarter of 2022 were $29.9 million compared to $7.2 million for the same period in 2021. The increase of $22.7 million was primarily due to the expense of prepaid balances related to consumables and manufacturing reservations, as the balances were evaluated and deemed to have no future value ($25.2 million). This increase was partially offset by lower costs associated with manufacturing ($2.5 million).
G&A Expenses: General and administrative expenses for the second quarter of 2022 were $15.6 million compared to $6.8 million for the same period in 2021. The increase of $8.8 million was primarily due to an increase in legal expense ($10.3 million). This increase was driven by the preliminary settlement of the securities and derivative litigation, net of expected insurance recovery ($8.6 million), related legal fees ($0.9 million), legal fees related to the internal review ($0.3 million), and other legal expenses ($0.5 million). This increase was partially offset by a decrease in marketing and commercial expenses, which were incurred in the second quarter of 2021 in preparation for potential commercial launch of Vicineum but were discontinued as a result of the Complete Response Letter from the FDA received in August 2021 ($1.5 million).
Non-Cash Related Expenses:
Intangibles impairment charge for the second quarter of 2022 was $27.8 million. In light of assumption changes in market share for Vicineum and the Company’s strategic decision to voluntarily pause further development of Vicineum in the US, the Company performed an interim impairment test for In-Process Research and Development (IPR&D) assets and goodwill. This resulted in the full impairment of IPR&D assets ($14.7 million) and goodwill ($13.1 million).
The change in the fair value of contingent consideration was a decrease of $37.3 million for the second quarter of 2022, compared to an increase of $13.6 million for the same period in 2021. This decrease was due to a change in projected net sales for Vicineum subject to contingent consideration liability, which was based upon projected net sales in the Greater China region in the second quarter of 2022 compared to projected net sales worldwide in the second quarter of 2021.
Income Tax Benefit: Benefit from income tax was $3.9 million for the second quarter of 2022. In connection with the intangibles impairment charge for the second quarter of 2022, the Company wrote-down the associated deferred tax liability by $4.0 million as a benefit. This was partially offset by $0.1 million in income tax paid to foreign jurisdictions pursuant to the Company’s license agreement with Qilu Pharmaceutical. There was no tax benefit or provision in the second
quarter of 2021.
Net Loss: Net loss was $32.0 million, or $0.16 per basic and per diluted share, for the second quarter of 2022, compared to net loss of $25.4 million, or $0.15 per basic and diluted share, for the same period in 2021. The change was primarily attributable to increases in R&D and G&A expenses ($31.5 million), primarily driven by the reduction of prepaid balances related to consumables and manufacturing reservations and the preliminary settlements of the securities and derivative litigation. Additionally, license and related revenue recognized decreased ($2.2 million). This was partially offset by favorable changes in non-cash related expenses of $27.0 million (including tax benefit).
About Vicineum

Vicineum, a locally administered fusion protein, is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A. Vicineum is constructed with a stable, genetically engineered peptide tether to ensure the payload remains attached to the antibody binding fragment until it is internalized by the cancer cell. This fusion protein design is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical trials conducted by Sesen Bio, EpCAM has been shown to be overexpressed in non-muscle invasive bladder cancer (NMIBC) cells with minimal to no EpCAM expression observed on normal bladder cells. Sesen Bio has completed the follow-up stage of a Phase 3 clinical trial in the US for the treatment of BCG-unresponsive NMIBC. In February 2021, the FDA accepted the Company’s Biologics License Application (BLA) file for Vicineum for the treatment of BCG-unresponsive NMIBC, granted Priority Review for the BLA and set a Prescription Drug User Fee Act (PDUFA) date of August 18, 2021. On August 13, 2021, the Company received a Complete Response Letter (CRL) from the FDA regarding its BLA for Vicineum. On July 18, 2022, Sesen Bio announced that it had made the strategic decision to voluntarily pause further development of Vicineum in the US. The decision was based on a thorough reassessment of Vicineum, which included the incremental development timeline and associated costs, following recent discussions with the FDA. The Company continues to believe that Vicineum has benefits for patients and healthcare providers that can be maximized through a company with a larger infrastructure, and as such intends to seek a partner for further development of Vicineum while it continues to assess potential strategic alternatives with the goal of maximizing shareholder value. Additionally, Sesen Bio believes that cancer cell-killing properties of Vicineum promote an anti-tumor immune response that may potentially combine well with immuno-oncology therapies, such as checkpoint inhibitors. For this reason, the activity of Vicineum in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.

On August 8, 2022 Harbour BioMed (the "Company", HKEX: 02142) reported that the preclinical results of porustobart (HBM4003, or the HCAb 4003-2 in the research paper), a next-generation fully human heavy-chain antibody with a Treg depletion mechanism, were published in the Proceedings of the National Academy of Sciences (PNAS) (Press release, Harbour BioMed, AUG 8, 2022, View Source [SID1234617825]). For the last two years, the Company’s scientists have published paper on top-tier journals such as Nature Communications, Science Immunology, and now PNAS.

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Porustobart with a unique molecular structure shows an excellent preclinical efficacy and safety profile:

1. A fully human heavy-chain antibody (HCAb), porustobart binds human CTLA4 with high affinity reaching 10-11 M.

2. It effectively depletes tumor-resident Treg with enhanced antibody-dependent cellular cytotoxicity (ADCC).

Porustobart showed, maximally, 60% lysis of in vitro differentiated Treg cells at 1 nMol concentration. The median effective concentration of porustobart was about 100-fold more potent than the current standard antibody.

3. It shows potent tumor penetration due to its small size, resulting in a more widely effect on T cell activation.

Mice were dosed with labeled porustobart or hIgG1. Peak signal was detected at 1h in normal tissues, while it was maximal at 24h in the tumor, showing superior tumor penetration for porustobart than hIgG1.

4. Less systemic drug exposure in vivo potentially provides an improved therapeutic window in clinical applications.

In MC38-bearing human CTLA-4 knock-in (KI) C57BL/6 mice and CT26-bearing huCTLA-4 KI Balb/c mice, porustobart showed higher potency than the standard anti CTLA4 antibody.

More importantly, porustobart showed an excellent safety profile. A single dose of porustobart at 30 mg/kg was well tolerated in cynomolgus monkeys.

About PNAS

PNAS is one of the world’s most-cited and comprehensive multidisciplinary scientific journals. The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), is an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.

About Porustobart (HBM4003)

Porustobart (HBM4003) is a fully human anti-CTLA-4 heavy chain antibody (HCAb) generated in Harbour Mice. It is the first fully human heavy chain antibody entered into clinical stage globally. By enhancing antibody-dependent cell cytotoxicity (ADCC) killing activity, porustobart demonstrates significantly improved depletion of high CTLA-4 expressing Treg cells in tumor tissues. The potent anti-tumor efficacy and differentiated pharmacokinetics with durable pharmacodynamic effect present a favorable product profile. This novel and differentiated mechanism of action has the potential to improve efficacy while significantly reducing the toxicity of the drug in monotherapy and combination therapy.

On August 8, 2022 As a result of recent research revealing that a significant number of colorectal cancer patients with actionable variants are missed under previous genetic testing guidelines, the National Comprehensive Cancer Network (NCCN) reported that new guidelines calling for testing to be available to all patients diagnosed with colorectal cancer (Press release, Invitae, AUG 8, 2022, View Source [SID1234617763]). Specifically, NCCN recommended that germline multigene panel testing should be offered to all individuals with CRC age <50 and be considered for all others, particularly for, but not restricted to, those with evidence of mismatch repair in their tumor or suggestive family history. These new recommendations expand the current testing criteria, which limited testing to certain age groups and types of cancer.

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Invitae’s (NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. www.invitae.com (PRNewsFoto/Invitae Corporation)

The new NCCN guidelines follow recent landmark studies published in JAMA Oncology and Clinical Gastroenterology and Hepatology by Invitae and Mayo Clinic supporting universal genetic testing for all cancer patients, regardless of cancer type, age, stage or family history. The data showed that nearly 1 in 6 colorectal cancer patients had inherited gene mutations that increased their risk of cancer. Additionally, more than 10% of patients in the study had changes to their cancer treatments based on genetic testing findings – many of whom would have been missed by previous limited testing guidelines. The study also found that patients diagnosed with colorectal cancer at a younger age were more likely to have heritable genetic changes linked to an increased risk of cancer.

The new NCCN guidelines have the potential to impact millions, as colorectal cancer is the third most diagnosed cancer and an estimated 5 million people worldwide currently live with colorectal cancer according to the American Cancer Society. The lifetime risk of developing colorectal cancer according to ACS is about 1 in 23 for men and 1 in 25 for women, and there’s recently been an increase in incidence among people younger than 50 years old. Understanding risk and implementing screening strategies is essential to early detection and better outcomes for patients.

"As the medical community’s understanding of genetic links to cancer evolves, genetic testing guidelines must evolve with it," said Robert Nussbaum, M.D., chief medical officer of Invitae, who co-authored a letter in January 2022 to the NCCN formally requesting universal germline testing for patients with CRC be added to their guidelines. "In addition to excluding older people from receiving access to medically actionable information about their disease, previous guidelines were based on studies with an overrepresentation of individuals of European origin, potentially biasing and exacerbating existing disparities to those of non-European background."

"The number of genes with targeted therapeutic or clinical management implications for colorectal cancer has significantly increased in recent years," Dr. Nussbaum continued. "At the same time, genetic testing has become more affordable. These new guidelines will help identify more patients and their family members who might benefit from genetic assessment."

"The INTERCEPT study supports the use of universal germline genetic testing for patients with colorectal cancer, and has shown the clinical impact of this strategy in targeted therapy implementation, personalized clinical management and cascade family testing for prevention. The NCCN update will improve access for patients with colorectal cancer to the gene-directed precision care they need," Jewel Samadder, M.D., enterprise co-leader precision/individualized cancer medicine, Mayo Clinic Comprehensive Cancer Center.

In addition to recommending testing be either offered or considered for all diagnosed colorectal cancer patients, the NCCN guidelines recommend subsequent cascade testing of family members of colorectal cancer patients who have pathogenic variants identified in cancer risk genes. "This is one of the biggest challenges related to germline multigene panel testing for all colorectal cancer patients," explained Ed Esplin, M.D., Ph.D., FACMG, FACP, clinical geneticist at Invitae and a co-author of the INTERCEPT study. "Alerting other family members to be tested to determine increased risk and implementing more intensive surveillance could lead to earlier diagnosis, significantly higher chance of curative treatment and ultimately, prevention of colorectal cancer entirely for those at increased risk."

On August 8, 2022 Atreca, Inc. (Atreca) (NASDAQ: BCEL), a clinical-stage biotechnology company focused on developing novel therapeutics generated through a unique discovery platform based on interrogation of the active human immune response, reported financial results for the second quarter ended June 30, 2022 and provided an overview of recent developments (Press release, Atreca, AUG 8, 2022, View Source [SID1234617779]).

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"While we took steps during the second quarter to extend our cash runway through the end of 2023, we remain committed to the development of ATRC-101 and ATRC-301, as well as the advancement of our earlier-stage pipeline and the discovery of additional novel tumor-targeting lead antibodies using our platform. This is underscored by our hiring of Dr. Stephen Gould as Atreca’s new Chief Scientific Officer," said John Orwin, Chief Executive Officer of Atreca. "We are looking forward to an eventful second half of 2022, as we anticipate reporting updated data from the monotherapy and pembrolizumab combination arms of our Phase 1b clinical trial of ATRC-101, as well as initial toxicology data from our second clinical candidate, ATRC-301."

Recent Developments and Highlights

In June 2022, Atreca appointed Stephen Gould, Ph.D. as Chief Scientific Officer. Dr. Gould joined Atreca following 15 years at Genentech, where he most recently served as Executive Director, Translational Oncology leading a team focused on developing tumor-specific antibodies weaponized with immune-targeting arms or drug payloads for use in both hematologic and solid tumors, including two approved oncology therapeutics.

Enrollment of participants based on ATRC-101 target expression in archival or newly obtained biopsies is ongoing in the Phase 1b clinical trial. To date, 62 total participants have been enrolled in the monotherapy and pembrolizumab-combination cohorts of the trial. Atreca expects to report updated data from the trial in the second half of 2022.

In addition, Atreca has initiated manufacturing activities for the ATRC-301 program to support filing an IND planned for late 2023, and Atreca anticipates reporting preliminary toxicology data in the second half of 2022.

Second Quarter 2022 Financial Results

As of June 30, 2022, cash and cash equivalents and investments totaled $101.7 million.
Research and development expenses for the quarter ended June 30, 2022, were $20.0 million, including non-cash share-based compensation expense of $2.6 million.
General and administrative expenses for the three months ended June 30, 2022, were $8.1 million, including non-cash share-based compensation expense of $2.8 million.
Atreca reported a net loss of $27.9 million, or basic and diluted net loss per share attributable to common stockholders of $0.72, for the three months ended June 30, 2022.

On August 8, 2022 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in the field of cellular metabolism pioneering therapies for genetically defined diseases, reported the grant of inducement equity awards outside of the company’s 2013 Stock Incentive Plan to its newly appointed chief executive officer, Brian Goff (Press release, Agios Pharmaceuticals, AUG 8, 2022, View Source [SID1234617795]). The grants were approved by the board of directors effective as of August 8, 2022 as inducements material to Mr. Goff entering into employment with the company in accordance with Nasdaq Listing Rule 5635(c)(4).

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The inducement grants consisted of (i) a nonstatutory option to purchase up to 561,083 shares of common stock, (ii) restricted stock units for 68,073 shares of common stock and (iii) performance stock units for 170,183 shares of common stock. The option has an exercise price of $29.38 per share, the closing price per share of the company’s common stock as reported by Nasdaq on August 8, 2022. The option has a ten-year term and vests over four years, with 25% of the original number of shares vesting on the first anniversary of Mr. Goff’s start date and 2.0833% of the shares underlying the options vesting monthly thereafter, subject to his continued service with the company through the applicable vesting dates. Each restricted stock unit will entitle Mr. Goff to receive one share of the company’s common stock for each restricted stock unit that vests. The restricted stock units will vest in equal annual installments on each anniversary of Mr. Goff’s start date, until the third anniversary of such date, subject to his continued service with the company through the applicable vesting dates. Each performance stock unit represents a contingent right to receive one share of the company’s common stock upon the achievement of specified performance milestones.