On November 9, 2021 Selecta Biosciences, Inc. (NASDAQ: SELB), a biotechnology company leveraging its clinically validated ImmTOR platform to develop tolerogenic therapies that selectively mitigate unwanted immune responses, reported financial results for the third quarter ended September 30, 2021 and provided a business update (Press release, Selecta Biosciences, NOV 9, 2021, View Source [SID1234594803]).

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"The third quarter of 2021 was filled with many significant advancements that further validated the value and breadth of our innovative ImmTOR platform, including important milestones across our pipeline and the establishment of numerous collaborations that will continue to propel us forward in the year ahead," said Carsten Brunn, Ph.D., president and chief executive officer of Selecta. "We recently presented topline data from the empty AAV8 capsid study, SEL-399 in healthy volunteers. We believe this pioneering proof-of-concept study showed for the first time ImmTOR’s potential to address one of the biggest limitations in gene therapy: preventing the formation of anti-AAV8 neutralizing antibodies after ImmTOR treatment with AAVs and enabling re-dosing of life-saving gene therapies. We are excited to build on these exciting findings, which will inform our clinical development strategy and bring hope to those patients suffering from monogenic disease. We continue to prosecute our clinical pipeline, execute value accretive business development with world class partners and add talent and depth to our leadership team."

Recent Highlights and Anticipated Upcoming Milestones:
Enzyme Therapies:

SEL-212 for chronic refractory gout: Enrollment for the Phase 3 DISSOLVE clinical program for the treatment of chronic refractory gout, which was licensed to Sobi, is progressing as planned.
Topline data is expected in the second half of 2022.
ImmTOR with IgA1 protease for IgA nephropathy: Immunoglobulin A nephropathy (IgAN) is a leading cause of chronic kidney disease (CKD) and renal failure. Current treatments fail to address the root cause of the disease.
Investigational New Drug, or IND, enabling studies are underway. Selecta expects to file an IND in IgA nephropathy in 2022 and will provide additional updates.
Gene Therapies:

First-in-human trial of SEL-399: In collaboration with AskBio, Selecta initiated the first-in-human, dose-escalation trial of SEL-399, an adeno-associated viral serotype 8 (AAV8) empty vector capsid (EMC-101) containing no DNA combined with ImmTOR. The key objective was to determine the dose regimen of ImmTOR to effectively mitigate the formation of antibodies to AAV8 capsids used in gene therapies. Data was released on November 8, 2021. Key findings included:
No Serious Adverse Events were reported. All treatment-related adverse events were expected for ImmTOR, readily monitorable, and transient
At 30 days 6 of 6 or 100% of subjects that received 0.3 mg/kg of ImmTOR exhibited an anti-AAV8 neutralizing antibody titer of 1:25 or less. 4 of 6 or 67% of subjects at this dose had a titer of 1:5 or less
At 30 days 6 of 9 or 67% of subjects that received 0.15 mg/kg of ImmTOR exhibited an anti-AAV8 neutralizing antibody titer of 1:25 or less. 2 of 9 or 22% of subjects at this dose had a titer of 1:5 or less
At 90 days 2 of 6 subjects in the 0.3 mg/kg cohort were observed to have sustained control of neutralizing antibodies with titers of 1:25 or less
Consistent with preclinical data, we observed that the single dose ImmTOR cohorts saw delayed formation of neutralizing antibodies eventually reaching similar median levels of neutralizing antibodies to the control group by day 90
While most subjects treated with ImmTOR showed increases in antibody titers by Day 90, preclinical studies in mice and nonhuman primates indicate that if antibodies can be controlled at Day 30, we can maintain control with additional two monthly doses of ImmTOR.

SEL-302 for methylmalonic acidemia (MMA): IND filed for SEL-302 (MMA-101 in combination with ImmTOR), for the treatment of MMA, a rare metabolic disease in which the body cannot break down certain proteins and fats.
IND filed in Q3 2021, 30-day FDA review period has expired.
FDA has orally communicated they are still considering certain aspects of the submission related to chemistry, manufacturing and control, or CMC.
Formal FDA decision on IND expected by the end of November.
SEL-313 for ornithine transcarbamylase deficiency (OTC deficiency): Selecta’s proprietary gene therapy product candidate, SEL-313, is being developed to treat OTC deficiency, a rare genetic urea cycle disorder that causes ammonia to accumulate in the blood due to mutations in the OTC gene.
SEL-313 is currently in preclinical development and a clinical trial application, or CTA, and/or IND filing are expected in 2022.
Restoring Self-Tolerance in Autoimmune Diseases:

Selecta continues IND-enabling work on an ImmTOR-based approach to treating primary biliary cholangitis (PBC) and expects to file an IND in PBC in the second half of 2022.
Corporate Updates:

Strategic Collaborations:
Gene Therapies
Takeda Pharmaceutical Company Limited ("Takeda"): Strategic licensing agreement to develop next-generation gene therapies in two lysosomal storage disorders. The collaboration leverages Selecta ImmTOR platform to enable redosing of transformative therapies.
Genovis: Strategic licensing agreement to advance a next-generation IgG protease. This partnership leverages Genovis’ proprietary and differentiated immunoglobulin G (IgG) protease, IdeXork (Xork), and Selecta’s ImmTOR platform to enable the dosing of transformative gene therapies in patients with pre-existing adeno-associated virus (AAV) immunity and treat certain IgG-mediated autoimmune diseases. Xork shows low crossreactivity to pre-existing antibodies in human sera. The combination of Xork with ImmTOR has the potential to address two of the biggest immunological challenges to gene therapy – expanding access to gene therapies by overcoming pre-existing antibodies to AAV and enabling vector re-dosing.
Enzymes
Ginkgo Bioworks ("Ginkgo"): Partnership to design novel enzymes and proteins with transformative therapeutic potential to advance treatments for orphan and rare diseases. This partnership leverages Ginkgo’s cell programing platform and Selecta’s ImmTOR platform to create transformative biologic and enzymatic therapies.
Autoimmune
Cyrus Biotechnology ("Cyrus"): Established protein engineering collaboration combining Selecta’s ImmTOR platform with Cyrus’ ability to radically redesign protein therapeutics. The lead program in the collaboration is a proprietary interleukin-2 (IL-2) protein agonist designed to selectively promote expansion of regulatory T cells (Treg) for the treatment of patients with autoimmune diseases and other deleterious immune conditions. The combination of ImmTOR with a Treg-selective IL-2 agonist has the potential to be a best-in-class therapeutic profile.
Leadership Expansion:
Kevin Tan was appointed as chief financial officer. Mr. Tan brings deep financial expertise and experience in the gene therapy and rare disease landscape. His impressive track record in capital management and financings, in both the biotech and investment sectors, will be invaluable as Selecta continues to pursue new partnership opportunities and advance multiple assets through the clinic.
Matthew Bartholomae was appointed as General Counsel, Board Secretary and transitioned from his previous role at Selecta as Associate General Counsel, Board Secretary.
Third Quarter 2021 Financial Results:

Cash Position: Selecta had $140.0 million in cash, cash equivalents, marketable securities, and restricted cash as of September 30, 2021, which compares to cash, cash equivalents, and restricted cash of $140.1 million as of December 31, 2020. Selecta believes its available cash, cash equivalents, marketable securities, and restricted cash will be sufficient to meet its operating requirements into the second quarter of 2023.

Net cash used in operating activities was $28.9 million for the nine months ended September 30, 2021, as compared to $42.1 million of cash provided by operating activities for the same period in 2020.
Revenue: Revenue for the third quarter of 2021 was $24.4 million, compared to $4.6 million for the same period in 2020. Revenue of $24.3 million was recognized under the license agreement with Sobi resulting from the shipment of clinical supply and the reimbursement of costs incurred for the Phase 3 DISSOLVE clinical program. The significant revenue increase is the result of the continued enrollment of the Phase 3 DISSOLVE clinical program that was initiated in the third quarter of 2020. Additionally, during the third quarter, Selecta recognized $0.2 million for shipments under the license agreement with Sarepta.

Research and Development Expenses: Research and development expenses for the third quarter 2021 were $21.0 million, which compares with $14.0 million for the same period in 2020. During the quarter ended September 30, 2021, there was an increase in expenses incurred for preclinical programs, salaries, headcount, and AskBio collaboration costs.

General and Administrative Expenses: General and administrative expenses for the third quarter 2021 were $5.4 million, which compares with $4.4 million for the same period in 2020. The increase in costs was primarily the result of salaries, professional fees, and stock compensation expenses.

Net loss: For the third quarter 2021, Selecta reported net loss of $17.9 million, or net loss per share of $0.16, compared to a net loss of $9.7 million, or net loss per share of $0.09 for the same period in 2020.

Conference Call and Webcast Reminder
Selecta management will host a conference call at 8:30 AM ET today to provide a corporate update and review the company’s third quarter 2021 financial results. Individuals may participate in the live call via telephone by dialing (844) 845-4170 (domestic) or (412) 717-9621 (international) and may access a teleconference replay for one week by dialing (877) 344-7529 (domestic) or (412) 317-0088 (international) and using confirmation code 10147803. Investors and the public can access the live and archived webcast of this call and a copy of the presentation via the Investors & Media section of the company’s website, www.selectabio.com.

On November 9, 2021 Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease with three ongoing Phase 1 clinical trials, reported the first clinical data from its Agonist Redirected Checkpoint (ARC) platform compounds, SL-172154 and SL-279252, in patients with advanced cancer (Press release, Shattuck Labs, NOV 9, 2021, View Source [SID1234594798]).

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For SL-172154 (SIRPα-Fc-CD40L), initial monotherapy Phase 1 dose-escalation data show favorable safety and tolerability for a CD40 agonist, high levels of CD47 target occupancy and CD40 target engagement, and escalating pharmacodynamic activity in heavily pretreated, platinum resistant ovarian cancer patients. For SL-279252 (PD1-Fc-OX40L), anti-tumor activity has been observed in heavily pretreated patients, including one confirmed partial response (PR), and a second unconfirmed PR, both in patients with PD-1/L1 inhibitor pretreated non-cutaneous melanoma. Both SL-172154 and SL-279252 have been well tolerated, and a recommended Phase 2 dose has not yet been identified. These data will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 36th annual meeting being held Wednesday, November 10, 2021, to Sunday, November 14, 2021. Additional data from both programs will be presented at the meeting and on an investor call on November 12, 2021.

"We are incredibly pleased to provide our first clinical update for our ARC fusion proteins, SL-172154 and SL-279252, which are both in Phase 1 dose-escalation trials," said Lini Pandite, MBChB, M.B.A., Chief Medical Officer of Shattuck. "The preliminary anti-tumor activity in the first-in-human dose escalation of SL-279252 in a heavily pretreated, PD-L1 unselected patient population, is highly encouraging. In addition, the tolerable safety profile, near-complete target occupancy of CD47 and target engagement of CD40, and compelling pharmacodynamic effects observed give us confidence that SL-172154 has now emerged as a differentiated CD47 inhibitor. Our observations of target occupancy and safety data to date suggests that we will not be limited in continuing dose escalation to identify a recommended Phase 2 dose with maximal pharmacodynamic activity. We are also pleased to report that the Investigational New Drug application is now open to expand clinical development of SL-172154 into studies in AML and HR-MDS."

SL-172154 Clinical Update

As of the data cut-off of July 6, 2021, 14 heavily pretreated, platinum resistant ovarian cancer patients with a median of five prior therapies were treated with intravenous administration of SL-172154 across four dose levels on two schedules: Schedule 1 (day 1, 8, 15, 29, Q2 weeks) at 0.1, 0.3 mg/kg and Schedule 2 (weekly) at 0.3, 1.0, 3.0 mg/kg.

SL-172154 has been well tolerated at all dose levels, with no dose-limiting toxicities reported. Low grade infusion-related reactions occurred in 53% of subjects, however all subjects have completed dosing. A maximum tolerated dose (MTD) has not been reached and dose escalation continues to 10 mg/kg.

The serum concentration of SL-172154 has increased through 3 mg/kg, as target engagement on both CD47 and CD40 has approached nearly 100%. The terminal elimination phase has not yet been characterized, likely due to target-mediated drug disposition. Significant dose-dependent increases in IL-12, along with post-dose increases in multiple other serum cytokines, including CCL2, CCL3, CCL4, and CCL22, and concurrent with rapid margination of CD40+ B cells and monocytes from the peripheral blood have been observed. Initial analysis of pre- and on-treatment tumor biopsies suggests that intravenous infusion of SL-172154 induces increases in multiple immune populations within the tumor microenvironment.

Anti-tumor activity of CD47 inhibitors is dependent upon the presence of a pro-phagocytic "eat me" signal, which can be provided by tumor-targeted antibodies with FcγR binding function, chemotherapy, or radiation. Based on our current understanding of the combined profile of SL-172154, we plan to begin a combination study with liposomal doxorubicin in patients with platinum resistant ovarian cancer in the first half of 2022. In addition, an IND is now open to study SL-172154 as monotherapy and in combination with azacitidine in HR-MDS and TP53 mutant AML patients, as well as in combination with azacitidine and venetoclax in patients with AML. The combined data from these trials will inform Shattuck’s global development strategy to progress SL-172154 to become the leading CD47- and CD40-targeted cancer immunotherapy.

SL-279252 Clinical Update

As of the data cut-off of June 11, 2021, 43 patients were enrolled and dosed intravenously with SL-279252 (median age 64 years; 56% male; median of 3 [range of 0-5] prior systemic therapies for metastatic disease). 30 patients were treated on Schedule 1 (day 1, 8, 15, 29, then every two weeks) from dose level 0.0001-6 mg/kg, and 13 patients were treated on Schedule 2 (weekly) from dose level 0.3-3 mg/kg. 58% of patients were previously treated with one or more PD-1/L1 inhibitors. Both PD-L1 and OX40 expression were low in available pre-treatment tumor biopsies. SL-279252 has been well tolerated, with no treatment-related dose-limiting toxicities reported to date. An MTD has not been reached.

Serum concentrations of SL-279252 have increased with dose, and the PK profile suggests that OX40 and PD-L1 binding approached saturating concentrations at the 6 mg/kg dose level. A preliminary half-life of ~23 hours has been observed. As a point of reference, the approved dose of PD-L1 blocking antibodies is approximately 10-15 mg/kg. Dose-dependent increases in post-treatment margination of OX40+CD4+ T cells was noted through 6 mg/kg and accompanied by a trend toward increasing numbers of CD8+ memory T cells in the peripheral blood. Post-treatment biopsies suggest that treatment with SL-279252 was associated with large increases in CD8+ cytolytic T cells in the tumors of some patients.

A confirmed PR was observed in a patient with metastatic ocular melanoma who had received five prior lines of therapy, including a PD-1 inhibitor. An unconfirmed PR was observed in a patient with mucocutaneous melanoma who had received therapy with anti-CTLA-4 and anti-PD-1 inhibitors. Stable disease was observed in an additional 12 patients, including six patients who experienced stable disease for greater than 24 weeks.

Dose escalation is ongoing using Schedule 1, at 12 mg/kg.

Shattuck Webcast Investor Meeting

Shattuck will host a conference call and webcast at 8:00 a.m. ET on Friday, November 12, 2021, to discuss the clinical data from SL-172154 and SL-279252 and to provide a general corporate update. Participants are invited to listen by dialing (833) 614-1555 (domestic) or (516) 575-8754 (international) five minutes prior to the start of the call and providing the passcode 4068596. A live webcast presentation will be available here or on the company’s website at www.ShattuckLabs.com under Events & Presentations. A replay of the webcast will be archived on the company’s website following the presentation.

About SL-172154

SL-172154 (SIRPα-Fc-CD40L) is an investigational ARC fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint interaction and activate the CD40 costimulatory receptor to bolster an anti-tumor immune response in patients with advanced cancers. Two Phase 1 clinical trials are ongoing, the first for patients with advanced and platinum resistant ovarian cancer (NCT04406623) and the second for patients with advanced squamous cell carcinoma of the head, neck or skin (NCT04502888).

About SL-279252

SL-279252 (PD1-Fc-OX40L) is an investigational ARC fusion protein designed to simultaneously inhibit the PD-1/PD-L1 checkpoint interaction and activate the OX40 costimulatory receptor to bolster an anti-tumor immune response receptor in patients with advanced solid tumors. A Phase 1 trial in patients with solid tumors and lymphoma is ongoing (NCT03894618).

On November 9, 2021 Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease with three ongoing Phase 1 clinical trials, reported financial results for the third quarter ended September 30, 2021, and provided recent business highlights (Press release, Shattuck Labs, NOV 9, 2021, View Source [SID1234594797]).

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"We designed the ARC platform to simultaneously block immune checkpoint targets and activate immune costimulatory receptors in the TNF superfamily. The clinical data presented this week at SITC (Free SITC Whitepaper) demonstrate evidence of anti-tumor activity, target receptor binding, and dose-dependent immune activation specific to each of CD40 and OX40," said Taylor Schreiber, M.D., Ph.D., and Chief Executive Officer of Shattuck. "Both compounds have been well tolerated and are demonstrating predictable dose-response relationships in humans. The doses we have explored to date remain below the recommended Phase 2 doses of benchmark CD47 inhibitors and PD-L1 inhibitors, and we look forward to continuing dose escalation of both SL-172154 and SL-279252 into dose levels that we believe will maximize the pharmacodynamic activity and anti-tumor activity of each compound."

"We are very encouraged by the initial data from the Phase 1 trial of SL-172154. The data show an excellent safety profile, high CD47 receptor occupancy and clear evidence of CD40 engagement, which collectively differentiate SL-172154 from other CD47 inhibitors," said Nehal Lakhani, M.D., Ph.D., South Texas Accelerated Research Therapeutics (START) Midwest, Grand Rapids, MI. "We desperately need new therapies for late-stage ovarian cancer patients, particularly in the platinum resistant setting. The combined actions of CD47 inhibition and CD40 activation provided by SL-172154 represents a strategy that has not yet been examined in this disease and may initiate anti-tumor immune responses that could provide lasting benefits in late-stage ovarian cancer."

"SL-172154 is emerging as a highly differentiated CD47 inhibitor. The clinical data indicate that this compound can safely engage CD40 in a manner that has evaded other CD40-targeted biologics for over twenty years. At the same time, we can compare and contrast the relative potency of CD40 versus OX40 activation, and the clinical data indicate that CD40 targeting provides substantially more immunologic activity than OX40 activation. There are some parallels to these observations in the checkpoint space, where blockade of targets like LAG3, TIM3, and TIGIT has been far more subtle than blockade of CTLA-4 or PD-1," continued Dr. Schreiber. "The current data suggests that we may be coming close to a recommended Phase 2 dose selection for SL-172154 as monotherapy. We are excited to transition to the combination with liposomal doxorubicin in ovarian cancer, and with azacitidine and venetoclax in AML, and azacitidine in higher-risk MDS and TP53 mutant AML. More importantly, these data help to establish the ARC platform more broadly as a novel class of biologic medicine, which opens opportunities for the rest of our vast pipeline of candidates developed internally at Shattuck."

Third Quarter 2021 Recent Business Highlights and Other Recent Developments

Agonist Redirected Checkpoint (ARC) Platform Clinical-Stage Pipeline

Initial Data from Ongoing SL-172154 (SIRPα-Fc-CD40L) Phase 1 Dose-Escalation Clinical Trial in Platinum Resistant Ovarian Cancer Demonstrate Favorable Safety Profile and High Target Occupancy at the 36th Annual SITC (Free SITC Whitepaper) Meeting: The Phase 1 trial is an open-label, multi-center, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154 administered intravenously in patients with platinum resistant ovarian cancer. Shattuck will continue dose escalation to 10mg/kg.

Data reported at SITC (Free SITC Whitepaper) was in 14 evaluable patients as of July 6, 2021, across four dose levels on two schedules: schedule 1 (day 1, 8, 15, 29, then every two weeks) at 0.1, 0.3 mg/kg and schedule 2 (weekly) at 0.3, 1.0, 3.0 mg/kg. To date, no dose limiting toxicities have been observed.
Preliminary pharmacodynamic parameters for SL-172154 demonstrate on-target, CD40-mediated immune activation. The binding of SL-172154 to CD40+ B cells and monocytes led to rapid activation and margination of these cells post infusion.
High target occupancy was observed on CD47+ leukocytes at the doses studied, with preferential binding to leukocytes as compared to red blood cells.
Cyclical increases in certain innate and adaptive serum cytokines were consistent with CD40 receptor engagement and activation following dosing. There were no notable increases in IL-6 or TNFα, or evidence of bell-shaped dose responses.
SL-172154 has been well tolerated at doses which achieve near-complete target occupancy for both CD40 and CD47, with evidence of on-target pharmacodynamic activity which has not yet plateaued, warranting further dose escalation.
Combination Study of SL-172154 with Liposomal Doxorubicin Expected to Begin First Half of 2022: A Phase 1B clinical trial of SL-172154 in combination with liposomal doxorubicin to evaluate safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamics is planned to begin enrolling in the first half of 2022. Shattuck continues to evaluate additional combination agents for SL-172154 for the treatment of patients with ovarian cancer.
Open IND for SL-172154 in AML and HR-MDS: Shattuck submitted an investigational new drug application to the U.S. Food and Drug Administration for a Phase 1A/B clinical trial for SL-172154 in patients with acute myeloid leukemia, or AML and, higher-risk myelodysplastic syndromes, or HR-MDS, in September. The IND is now open, and the trial will evaluate safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154, as both monotherapy and in combination. In AML, Shattuck plans to evaluate SL-172154 in combination with both azacitidine and venetoclax. In both HR-MDS and TP53 mutant AML, Shattuck plans to evaluate SL-172154 in combination with azacitidine. Initial data from the trial are expected in the second half of 2022.
Continued Enrollment of SL-172154 Phase 1 Clinical Trial in Squamous Cell Carcinoma of the Head and Neck or Skin: Shattuck continues to enroll patients in a Phase 1 clinical trial for SL-172154, in patients with squamous cell carcinoma of the head and neck or skin. The Phase 1 trial is evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154, administered intratumorally as monotherapy. Initial dose-escalation data from the trial are expected in the first half of 2022.
Initial Data from Ongoing SL-279252 (PD1-Fc-OX40L) Phase 1 Dose-Escalation Clinical Trial in Advanced Solid Tumors Demonstrate Evidence of Anti-Tumor Activity at the 36th Annual SITC (Free SITC Whitepaper) Meeting: The ongoing Phase 1 trial is an open-label, multi-center, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-279252 as monotherapy in patients with advanced solid tumors. Today, Shattuck reported continued enrollment at the next dose level, 12 mg/kg.

Data reported at SITC (Free SITC Whitepaper) as of June 11, 2021, was in 43 patients, dosed intravenously, with 30 patients treated on schedule 1 (day 1, 8, 15, 29, then every 2 weeks) from dose level 0.0001-6 mg/kg, and 13 patients treated on schedule 2 (weekly) from dose level 0.3-3 mg/kg. SL-279252 was well-tolerated in heavily pretreated subjects with refractory solid tumors with no maximum tolerated dose reached. A total of 16 patients were treated at doses of 1 mg/kg or higher on schedule 1.
Best response was one confirmed partial response (iPR) (ocular melanoma, four prior systemic regimens, including PD-1 and CTLA-4 inhibitors) in a patient who remained on treatment for more than one year, and stable disease (iSD) in 12 patients (including 1 unconfirmed iPR). iSD for > 24 weeks occurred in 5/12 patients.
58% of patients had received PD-1/L1 therapy, and of available tumor biopsies most tumors lacked PD-L1 expression as measured by TPS.
SL-279252 exhibited high OX40 target engagement and OX40-dependent PD effects.
Shattuck is currently enrolling patients with known PD-L1 positive tumors at dose levels of 12 mg/kg, to fully characterize PK, PD, and anti-tumor activity.
Corporate Updates

Shattuck and Takeda Mutually Agree to Termination of Collaboration Agreement: In November 2021, Shattuck and Takeda mutually agreed to termination of the Collaboration Agreement for SL-279252 and SL-115154, originally executed in 2017. Shattuck is no longer required to satisfy any remaining performance obligations, the Company will not make any payments to or receive any future milestone or royalty payments from Takeda, and all options to license and rights of first negotiation held by Takeda under the Collaboration Agreement were terminated.
Changes to Shattuck’s Board: In October 2021, Shattuck announced changes to its board of directors.

Dr. Carrie Brownstein was appointed to the board and serves as a member of the Nominating and Corporate Governance Committee. Dr. Brownstein brings over 15 years of clinical research and development experience having held clinical leadership roles at Roche, Regeneron, Celgene and Cellectis and as a practicing pediatric hematologist oncologist.
Dr. George Golumbeski was appointed chairman of the Board. Dr. Golumbeski has served on Shattuck’s Board as an independent director since 2018. Dr. Golumbeski replaces Josiah Hornblower as chairman of the board. Mr. Hornblower resigned from the board in October 2021.
Third Quarter 2021 Financial Results

Cash Position: As of September 30, 2021, cash and cash equivalents and short-term investments were $290.2 million, as compared to $335.4 million as of December 31, 2020.
Research and Development (R&D) Expenses: R&D expenses for the third quarter ended September 30, 2021, were $15.1 million, as compared to $11.8 million for the third quarter ended September 30, 2020. The increase was primarily driven by increases in clinical development, personnel-related costs, and laboratory capabilities.
General and Administrative (G&A) Expenses: G&A expenses for the third quarter ended September 30, 2021, were $4.3 million, as compared to $2.5 million for the third quarter ended September 30, 2020. The increase was primarily driven by an increase in personnel related costs to support the operational expansion and costs associated with being a public company.
Net Loss: Net loss was $17.4 million for the third quarter ended September 30, 2021, or $0.41 per basic and diluted share, as compared to a net loss of $11.8 million for the third quarter ended September 30, 2020, or $1.54 per basic and diluted share.
2021 Financial Guidance

Shattuck believes its cash and cash equivalents and short-term investments will be sufficient to fund its operations into the second half of 2024, which is beyond results from its Phase 1 clinical trials of SL-172154 and SL-279252. The reduction in cash runway guidance from our last issued guidance is primarily attributable to increased clinical activities for SL-172154 and ongoing process development and manufacturing to support our ongoing and future clinical trials, including the development of a manufacturing process suitable for registrational trials. This cash runway guidance is based on the Company’s current operational plans and excludes any additional funding that may be received or business development or additional clinical development activities that may be undertaken.

About SL-172154

SL-172154 (SIRPα-Fc-CD40L) is an investigational ARC fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint interaction and activate the CD40 costimulatory receptor to bolster an anti-tumor immune response in patients with advanced cancers. Two Phase 1 clinical trials are ongoing, the first for patients with advanced and platinum resistant ovarian cancer (NCT04406623) and the second for patients with advanced squamous cell carcinoma of the head, neck or skin (NCT04502888).

About SL-279252

SL-279252 (PD1-Fc-OX40L) is an investigational ARC fusion protein designed to simultaneously inhibit the PD-1/PD-L1 checkpoint interaction and activate the OX40 costimulatory receptor to bolster an anti-tumor immune response receptor in patients with advanced solid tumors. A Phase 1 trial in patients with solid tumors and lymphoma is ongoing (NCT03894618).

On November 8, 2021 Xspray Pharma AB (publ) (Nasdaq Stockholm: XSPRAY) reported that the board of directors has resolved on a directed new share issue of 1,612,904 shares at a price of SEK 62 per share, corresponding to in total approximately SEK 100 million (Press release, Xspray, NOV 8, 2021, View Source [SID1234649574]).

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The board of directors of Xspray Pharma has, based on the authorisation granted by the annual general meeting on 20 May 2021, resolved on a directed new share issue of 1,612,904 shares. The subscription price in the directed new share issue is set to SEK 62 per share, which has been determined based on the volume-weighted average share price of Xspray Pharma’s share on Nasdaq Stockholm during the five-day period ending on 5 November 2021. The company receives approximately SEK 100 million through the directed new share issue.

The shares have been subscribed by Flerie Invest, a Swedish investment company in biotechnology and pharmaceuticals, founded by Thomas Eldered. As Xspray Pharma has chosen to increase its focus on the improved version of dasatinib, Dasynoc , the proceeds from the share issue will mainly be used to strengthen the development of the company’s presence in the US, primarily with the strategic marketing resources needed for the market launch of Dasynoc. Resources will also be invested in accelerating the development of the fast-growing portfolio.

"Xspray Pharma has a very promising and growing product portfolio where Dasynoc is now facing the application for market approval at the same time as HyNap-Nilo will undergo studies and registration-based studies. Several products in the early phase will also reach the clinical development stage within the next year. It is of course very gratifying that Flerie Invest, in this important phase for Xspray Pharma, chooses to invest in the company. Flerie Invest is a specialized and long-term investor whose management has a deep and broad competence and experience in commercial pharmaceutical production. They also have a very strong network of contacts in the global pharmaceutical industry. Flerie Invest will be a very valuable addition to Xspray Pharma’s shareholder base", says Per Andersson, CEO of Xspray Pharma.

"We have been following Xspray Pharma for a long time and are impressed with the potential in the company’s unique technology. The recently decided focus on improved PKIs, and not pure generics, makes the company even more interesting. The improved drugs have the potential to provide fewer side effects and better effects and thus constitute essential therapies for affected patients. We therefore look forward to being involved in the company’s continued development", comments Thomas Eldered, founder and board member of Flerie Invest.

The board of directors has resolved on the issue by utilizing the authorisation granted by the annual general meeting and the reason for the deviation from the shareholders’ preferential rights is that the board of directors considers that the investment from Flerie Invest is for Xspray Pharma, and thus for its shareholders, the most advantageous way to raise capital in a time and cost-efficient manner and in the meanwhile onboarding a reputable, specialized and a long-term investor.

In its deliberations, the board of directors has further taken into account that there are no time- and cost-effective ways to successfully carry out a rights issue on terms favorable to the company, that the subscription price negotiated with Flerie Invest at arm’s length is not discounted but has been based on the volume-weighted average price of Xspray Pharma’s share during the five-day period ending on 5 November 2021, the last trading day before the issue resolution, and that Flerie Invest is not previously a shareholder in Xspray Pharma. The board of directors’ overall assessment is thus that there are good reasons to deviate from the preferential rights and carry out a directed new share issue.

Flerie Invest has, in connection with the share issue, agreed not to sell any shares in Xspray Pharma during a lock-up period of 360 days, subject to customary exceptions. In connection with the share issue, Xspray Pharma has agreed to a lock-up undertaking, with customary exceptions, on future share issuances for a period of 90 days.

Through the directed new share issue, the total number of shares and votes will increase by 1,612,904, from 19,067,504 to 20,680,408, which corresponds to a dilution of approximately 7.8 percent based on the total number of shares and votes in Xspray Pharma after the directed new share issue. The share capital increases with SEK 1,612,904, from SEK 19,067,504 to SEK 20,680,408.

Xspray Pharma has, in connection with the directed new share issue, appointed Advokatfirman Vinge as legal advisor.

On November 8, 2021 Kronos Bio, Inc, a company dedicated to transforming the lives of those affected by cancer, and Tempus, a leader in artificial intelligence and precision medicine, reported a multi-year collaboration that provides Kronos Bio with access to Tempus’ real-world genomic and transcriptomic data and data analytics tools (Press release, Kronos Bio, NOV 8, 2021, View Source [SID1234643240]).

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Under the agreement, Kronos Bio will have access to a number of precision medicine tools, including Tempus’ modeling lab, which houses a growing repository of molecularly profiled organoids. Access to such data and tools will help Kronos Bio accelerate the preclinical and clinical development of its current and future portfolio, by for example, using organoid models to generate biomarker hypotheses that can be tested in the clinic or in virtual molecularly defined patient cohorts drawn from Tempus’ extensive data sets.

The collaboration builds on an earlier agreement announced in February under which Tempus is performing molecular characterization of tumor samples from patients enrolled in Kronos Bio’s Phase 1/2 clinical study of the company’s CDK9 inhibitor KB-0742. Tempus will retrospectively sequence and analyze these patient samples to assess the relationship between MYC copy number, MYC expression levels and clinical response. Tempus will also explore a path to developing a companion diagnostic.

The expanded relationship leverages Kronos Bio’s deep expertise in transcriptional regulation and Tempus’ next-generation-sequencing capabilities, as well as drawing on each company’s computational biology capabilities. Kronos Bio also has the option to join Tempus’ TIME Trial Network, which supports rapid patient identification, site activation and enrollment of select clinical trials.

"With a shared commitment to improving patient outcomes, we are building upon our existing work with Kronos Bio to advance the company’s portfolio of clinical programs, including lanraplenib and KB-0742," said Marc Yoskowitz, executive vice president and chief strategy officer for Life Sciences at Tempus. "We look forward to harnessing the strength of our entire platform to support the discovery and development of novel cancer therapeutics."

The capabilities provided under the expanded agreement offer Kronos Bio the opportunity to access real-world data to further refine current understanding of transcription regulatory networks (TRNs), which could help accelerate clinical development.

"This partnership will bring together Kronos Bio’s knowledge and experience with transcriptional regulatory networks and Tempus’ sequencing expertise and exceptional data analytics tools and organoid models," said Jorge DiMartino, M.D., Ph.D., chief medical officer and executive vice president, Clinical Development at Kronos Bio. "We are looking forward to working together now and in the future, as we continue to progress our current clinical candidates, test rational combinations, and bring forward new ones, with the goal of getting medicines to patients as quickly as possible."