8-K
0001566373false00015663732021-11-122021-11-12

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): November 12, 2021

 

F-STAR THERAPEUTICS, INC.

(Exact name of Registrant as Specified in Its Charter)

 

 

Delaware

001-37718

52-2386345

(State or Other Jurisdiction

of Incorporation)

(Commission File Number)

(IRS Employer

Identification No.)

 

Eddeva B920 Babraham Research Campus

Cambridge, United Kingdom

CB22 3AT

(Address of Principal Executive Offices)

 

+44-1223-497400

Registrant’s Telephone Number, Including Area Code

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class

 

Trading

Symbol(s)

 

Name of each exchange on which registered

Common stock, $0.0001 par value

 

FSTX

 

 

The Nasdaq Stock Market

(Nasdaq Capital Market)

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.

 

 

 


 

Item 8.01. Other Events.

On November 12, 2021, F-star Therapeutics, Inc. (“F-star”) issued a press release announcing a poster presentation of preclinical data on FS120 combination with PD-1, a first-in-class dual-agonist tetravalent bispecific antibody targeting OX40 and CD137, at the 36th annual Society for Immunotherapy of Cancer (“SITC”) 2021 Conference, taking place in Washington, D.C. on November 12-14, 2021. At the SITC 2021 Conference, F-star will be presenting a poster titled “FS120, an OX40/CD137 tetravalent bispecific dual agonist antibody, synergistically increases the antitumor activity of anti-PD-1 in preclinical studies.” In the press release, F-star announced that Michelle Morrow, Ph.D., Vice President, Preclinical Translational Pharmacology, will also speak at the SITC 2021 Conference on Sunday, November 14, during Session 300: Novel Bispecifics, on “Dual Checkpoint Bispecifics: Next Generation Cancer Therapy to Overcome Immune Evasion”. A copy of each of the press release and the poster are attached hereto as Exhibits 99.1 and 99.2, respectively, and each is incorporated herein by reference.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits

The following exhibit is furnished with this report:

 

Exhibit

Number

 

Description

99.1

 

Press release dated November 12, 2021.

99.2

 

Poster #573, titled “FS120, an OX40/CD137 tetravalent bispecific dual agonist antibody, synergistically increases the antitumor activity of anti-PD-1 in preclinical studies”.

104

 

Cover Page Interactive Data File (embedded within the Inline XBRL document)

 

* Filed herewith.

 

2


 

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.

 

 

 

 

F-STAR THERAPEUTICS, INC.

 

 

 

 

Date: November 12, 2021

 

 

/s/ Darlene Deptula-Hicks

 

 

 

Name: Darlene Deptula-Hicks

 

 

 

Title: Chief Financial Officer

 

3


EX-99.1

 

Exhibit 99.1

https://cdn.kscope.io/d8d221b3955403239fdf9504158752e8-img222233780_0.jpg 

 

F-star Therapeutics to Present at The Society for Immunotherapy of Cancer (SITC) 2021 Conference

 

Dr. Michelle Morrow to present on F-star’s Proprietary Bispecific Platform including FS118, our LAG-3/PD-L1 Bispecific

 

Poster Presentation of Preclinical Data Demonstrates Potential for F-star’s FS120 First-in-Class OX40/CD137 Tetravalent Dual T Cell Agonist in Combination with Anti-PD-1

 

CAMBRIDGE, United Kingdom and CAMBRIDGE, Mass.- November 12, 2021—(Globe Newswire) F-star Therapeutics, Inc. (NASDAQ: FSTX), a clinical-stage biopharmaceutical company dedicated to developing next generation bispecific immunotherapies to transform the lives of patients with cancer, today announced that the Company is participating in the 36th annual Society for Immunotherapy of Cancer (SITC) 2021 Conference, taking place November 12-14 in Washington, D.C.. F-star’s Michelle Morrow, Ph.D., will speak at 9:15 a.m. on Sunday, November 14, during Session 300: Novel Bispecifics, on Dual Checkpoint Bispecifics: Next Generation Cancer Therapy to Overcome Immune Evasion. We are also excited to announce that Matthew Lakins Ph.D , is lead author on a poster presentation 573 on preclinical data for FS120 combination with PD-1, a first-in-class dual-agonist tetravalent bispecific antibody targeting OX40 and CD137. FS120 is currently being evaluated in a Phase 1 monotherapy dose escalation clinical trial (NCT04648202) which aims to identify a well tolerated and pharmacologically active dose of FS120 for exploration in future clinical studies as monotherapy, and in combination with other agents.

In her presentation, Dr. Morrow explains how bispecific antibodies can unlock new biology via mechanisms that combination approaches cannot. F-star’s FS118 is a dual checkpoint inhibitor targeting PD-L1 and LAG-3 that drives LAG-3 shedding and receptor down-regulation, via bispecific activity. It is one of a range of dual antagonist bispecific formats that are being explored in clinical development, each with the potential to elicit unique biological activity which may translate to different clinical outcomes. FS118 is designed to provide unique pharmacology, causing a dose-dependent increase of soluble LAG-3, and potentially offering a more durable response in patients.

In the Phase 1 clinical trial, FS118 was well tolerated with no treatment-related serious adverse events and no dose-limiting toxicity, up to 20mg/kg. In addition to the ongoing checkpoint inhibitor relapsed head and neck cancer study, that is anticipated to report data in mid-2022, F-star is initiating a clinical trial in checkpoint inhibitor naïve, biomarker enriched NSCLC and DLBCL patients in order to broaden the clinical reach of this exciting LAG-3 & PD-L1 targeting bispecific antibody.

Michelle Morrow, Ph.D., Vice President, Preclinical Translational Pharmacology, F-star states, “Checkpoint inhibitors have changed the way we now think about treating patients with cancer and a

 


 

new wave of target combinations looks to build on current success. Bispecific dual checkpoint inhibitors have the potential to further improve on the clinical outlook for patients as a next generation of treatments. At F-star, we have designed bispecific antibodies that may enable focused, potent and safe immune activation through crosslinking, clustering and conditionality.”

 

Key findings from poster presentation on FS120 include:

 

FS120 in combination with anti-PD-1 (pembrolizumab) was shown to enhance T cell activity in multiple human primary immune assays. In combination with an anti-PD-1, FS120 surrogate increased antitumor efficacy in a mouse tumor model with pharmacodynamic changes related specifically to T cell activation, when compared to monotherapies, either alone or in combination.

 

These data support the development of FS120 in combination with Keytruda in patients with cancers that are resistant to checkpoint inhibitor therapy.

Neil Brewis, Ph.D., Chief Scientific Officer, F-star notes, “We continue to be encouraged by this additional mechanistic preclinical data on FS120 demonstrating the potential for FS120 to increase antitumor activity of anti-PD-1 in patients with cancer. Our Phase 1 dose escalation study is ongoing to determine a well tolerated and optimal dosing regimen to initiate the KEYTRUDA combination.”

About FS120

In early clinical studies, agonist antibodies targeting the T cell costimulatory receptors OX40 or CD137 have shown immune-stimulatory effects. FS120 is a first-in-class tetravalent bispecific dual agonist antibody incorporating OX40 binding into the Fc-region (termed an Fcab) and CD137 Fabs in a natural human IgG1 antibody and with silenced FcγR activity for reduced toxicity, as shown in preclinical safety studies. FS120 crosslinks and clusters both receptors eliciting a robust immune stimulation and, in the case of FS120 surrogate, robust antitumor activity in mouse tumor models, independent of FcγR crosslinking1. FS120 has the potential to deliver tumor-agnostic clinical efficacy with good tolerability.

About F-star Therapeutics, Inc.

F-star Therapeutics, Inc. is a clinical-stage biopharmaceutical company dedicated to developing next generation immunotherapies to transform the lives of patients with cancer. F-star is pioneering the use of tetravalent (2+2) bispecific antibodies to create a paradigm shift in cancer therapy. The Company has four second-generation immuno-oncology therapeutics in the clinic, each directed against some of the most promising IO targets in drug development, including LAG-3 and CD137. F-star’s proprietary antibody discovery platform is protected by an extensive intellectual property estate. F-star has over 500 granted patents and pending patent applications relating to its platform technology and product pipeline. The Company has attracted multiple partnerships with biopharma targeting the significant unmet needs across several disease areas, including oncology, immunology, and CNS.

For more information visit website and follow us on LinkedIn and Twitter.

Forward Looking Statements

Certain statements contained in this communication regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, known as the PSLRA. These

 


 

include statements regarding management’s intentions, plans, beliefs, expectations or forecasts for the future, and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. F-star undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise, except to the extent required by law. In some cases, you can identify forward-looking statements by terminology such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” or the negative of these terms or other comparable terminology, which are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such forward-looking statements are based on our expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including, but not limited to, the cash balances of F-star, the ability of F-star to remain listed on the Nasdaq Capital Market, F-star’s status as a clinical stage immuno-oncology company and its need for substantial additional funding in order to complete the development and commercialization of its product candidates, that F-star may experience delays in completing, or ultimately be unable to complete, the development and commercialization of its product candidates, that F-star’s clinical trials may fail to adequately demonstrate the safety and efficacy of its product candidates, that preclinical drug development is uncertain, and some of F-star’s product candidates may never advance to clinical trials, that results of preclinical studies and early stage clinical trials may not be predictive of the results of later stage clinical trials, that F-star relies on patents and other intellectual property rights to protect its product candidates, and the enforcement, defense and maintenance of such rights may be challenging and costly, and that F-star faces significant competition in its drug discovery and development efforts.

New factors emerge from time to time and it is not possible for us to predict all such factors, nor can we assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. These risks are more fully discussed in F-star’s Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and other documents filed from time to time with the SEC. Forward-looking statements included in this communication are based on information available to F-star as of the date of this communication. F-star does not assume any obligation to update such forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

For further information, please contact:

For investor inquiries
Lindsey Trickett
VP Investor Relations & Communications
+1 240 543 7970
lindsey.trickett@f-star.com

For media inquiries
Helen Shik
Shik Communications LLC
+1 617-510-4373

helen@shikcommunications.com

 

 


EX-99.2

 

Exhibit 99.2

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FS120, an OX40/CD137 tetravalent bispecific dual agonist antibody, synergistically increases the antitumor activity of anti-PD-1 in preclinical studies 1. FS120 MoA 5. Disease control T cell helper activity 4. PD-1 mAb blocks resistance 3. PD-1:PD-L1 immunosupression FS120 surrogate Upregulates T cell PD-1 Expression Mixed Lymphocyte Reaction (MLR) CD4+ T cell Assay (SEA) CD8+ Antigen Recall Assay (CEF) Antibody concentration (nM) Human IFNg (pg/mL) 0.001 0.01 0.1 1 10 100 0 2000 4000 6000 8000 Antibody concentration (nM) FS120 surrogate Upregulates T cell PD-1 Expression CD4+ CD8+ Figure 1. A FS120 and pembrolizumab combination mechanism of action hypothesis. B FS120 surrogate transiently upregulates PD-1 expression on T cells in the periphery when dosed at 10 mg/kg in a CT26 syngeneic tumor model Key Properties: • CD137 agonist with KD = 0.2 nM • OX40 agonist with KD = 0.2 nM • Dual conditional agonist activity dependent on coexpression of OX40 and CD137 in the tumor • Natural IgG format for ease of manufacture and Fc gamma binding null for safety 1. Activation of effector cells (CD8+ T cells and NK cells) 2. Stimulation of helper activity (CD4+ T cells) 3. Potentially decreases Treg activity, making them unstable and fragile Gaspar et al. Cancer Immunol Res June 1 2020 (8) (6) 781-793 | Papadopoulos et al. Annals of Oncology Vol32, Supp5, Sep 2021, Pages S864-S865 Figure 2. Combination activity of FS120 and anti-PD-1 (pembrolizumab) in human primary immune cell functional assays. A Human IFNγ release in a human MLR consisting of allogenic iDC and expanded CD4+ T cell co-cultured for 5 days, in response to isotype control, FS120, pembrolizumab or the combination. B Human IL-2 release on 4 days co-cultured expanded CD4+ T cell + iDC Staphylococcus aureus enterotoxin A (SEA) assay in response to isotype control, FS120, pembrolizumab or the combination. C Human IFNg release in HLA class II-restricted CEF peptide pool antigen recall assay in response to isotype control, FS120, pembrolizumab or the combination. Ctrl FS120 PD-1 mAb (pembrolizumab) 1 (pembrolizumab) 3. Combination Significantly Improves Survival Benefit Versus Either Monotherapy in a PD-1 mAb Refractory Tumor Model Figure 3. The combination of FS120 surrogate and anti-PD-1 mAb exhibits powerful synergy in a PD-1 mAb refractory syngeneic CT26 tumor model. A BALB/c mice were inoculated with 1x105 CT26.WT cells and were treated with control IgG, 1mg/kg FS120 surrogate, 10mg/kg anti-PD-1 mAb (clone: RMP 1-14) or the combination as indicated above. B, Combination treatment enhanced proliferating (Ki67+) CD8+ T cells in the blood, compared to either monotherapies, 6 days following treatment initiation. C Kaplan-Meier plot showing enhanced survival rate in combination group versus monotherapies 4. PD-1 mAb Lowers the Threshold for FS120 Surrogate Anti-tumor Activity Figure 4. The synergistic activity of combining FS120 surrogate and PD-1 mAb at different dose levels in mice. BALB/c mice were dosed with 10mg/kg PD-1 mAb and FS120 surrogate in the range of 0.1mg/kg to 10mg/kg 10 days after CT26 cell inoculation. The dosing plan was as descripted above in figure 3. A Kaplan-Meier plot for survival indicating a threshold change when adding PD-1 mAb in combination with FS120 surrogate. B Combination of FS120 surrogate and PD-1 mAb inhibits tumor growth to a greater extent compared to FS120 surrogate monotherapy, shifting the IC50 5. FS120 Surrogate Enhances Anti-PD-1 mAb Mediated Effector Cell Cytotoxicity Figure 5. Granzyme B expression by CD8+ T cells and NK cells from the periphery of CT26 tumor-bearing mice. CT26 tumor-bearing mice were dosed with isotype control, FS120 surrogate, PD-1 mAb or the combination. Blood PBMCs were collected on day 17 after inoculation. Cells were treated with protein transport inhibitor brefeldin A for 4 hours followed by flow cytometry staining and analysis. A Granzyme B expression by CD8+ T cells. B Granzyme B expression by NK cells. 6. Combination Induces a Strong, yet Transient, Proinflammatory Response Figure 6. The combination of FS120 surrogate and PD-1 mAb significantly, yet transiently, increased IFNg and IL-6 in serum from CT26 tumor-bearing mice. CT26 tumorbearing mice were treated with isotype control antibody, FS120 surrogate, PD-1 mAb or the combination as described in figure 3. Serum was analysed via meso scale discovery (MSD) for A mouse IFNg and B mouse IL-6. Representative graphs from assays performed in duplicate; data are presented as mean ± SEM. Conclusion FS120 combination with anti-PD-1 enhances T cell activity in multiple human primary immune assays. In combination with an anti- PD-1, FS120 surrogate increased the antitumor efficacy with pharmacodynamic changes related specifically to T cell activation, when compared to monotherapies. These data support the development of FS120 in combination with anti-PD-1 mAb in patients with cancer resistant to checkpoint therapy. FS120 is currently being evaluated in a Phase 1 monotherapy dose escalation trial (NCT04648202) which aims to identify a safe, tolerated and pharmacologically active dose of FS120 for exploration in future clinical studies as monotherapy, and in combination with other agents. Following determination of a safe and pharmacologically active dose, FS120 will be evaluated in combination with KEYTRUDA®, with the potential for early demonstration of clinical activity in specific tumor subtypes4. F-star expects to provide a progress update on the FS120 monotherapy accelerated dose titration cohorts later this year and plans to initiate the KEYTRUDA combination cohorts in the second half of 2022, following completion of the FS120 monotherapy dose escalation. ® KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp. SITC 2021 | 11 – 14 Nov | Poster Number: 573 1Oh et al, Cell 2020. Intratumoral CD4+ T cells mediate anti-tumour cytotoxicity in human bladder cancer https://doi.org/10.1016/j.cell.2020.05.017 2T reg fragility: A prerequisite for effective antitumor immunity? Curr Opin Immunol. 2016 doi: 10.1016/j.coi.2015.12.009 3T reg stability: to be or not to be. Cancer Immunol Res 2018. doi: 10.1158/2326-6066.CIR-18-0066. 4https://investors.f-star.com/news-releases/news-release-details/f-star-therapeutics-announces-collaboration-msd-evaluate-fs120 CD8+ T cell Proliferation Enhanced Survival Benefit mIFNg Control IgG PD-1 mAb FS120 surrogate ✱✱✱✱ ns Combination Control IgG PD-1 mAb FS120 surrogate ✱✱ ns Combination Days Post First Dose Days Post First Dose Control IgG PD-1 mAb FS120 Surrogate FS120 Surrogate + PD-1 mAb CD8+ T cells