8-K
false 0001566373 0001566373 2021-04-10 2021-04-10

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 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): April 10, 2021

 

 

F-STAR THERAPEUTICS, INC.

(Exact Name of Registrant as Specified in 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, and Zip Code)

 

+44-1223-497400

Registrant’s Telephone Number, Including Area Code

 

 

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 (see General Instruction A.2. below):

 

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)

 

(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 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2).

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 April 10, 2021, F-star Therapeutics, Inc. (the “Company”) issued a press release announcing a poster presentation of preclinical data from FS222, a tetravalent bispecific antibody targeting both CD137 and PD-L1 at the 2021 American Academy of Cancer Research (“AACR”) Annual Meeting, taking place virtually from April 10-15, 2021 and May 17-22, 2021. At the AACR 2021 Annual Meeting, the Company will be presenting a poster titled “FS222, a Tetravalent Bispecific Antibody Targeting CD137 and PD-L1, is Designed for Optimal CD137 Interactions Resulting in Potent T cell Activation Without Toxicity,” which became available via on-demand viewing on April 10, 2021. 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

 

Exhibit
Number
   Description
99.1    Press Release issued April 10, 2021.
99.2    Poster #1864, titled “FS222, a Tetravalent Bispecific Antibody Targeting CD137 and PD-L1, is Designed for Optimal CD137 Interactions Resulting in Potent T cell Activation Without Toxicity”.
104    Cover Page Interactive File (the cover page tags are embedded within the Inline XBRL document).


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 hereunto duly authorized.

 

      F-STAR THERAPEUTICS, INC.
Date: April 13, 2021      

/s/ Darlene Deptula-Hicks

      Darlene Deptula-Hicks
      Chief Financial Officer
EX-99.1

Exhibit 99.1

 

LOGO

F-star Therapeutics Shows Differentiation of FS222 in 2021 AACR Poster

Study Confirms F-star’s Bispecific Antibody Tetravalency is the Most Efficient Way to Induce Receptor Clustering and Activation

CAMBRIDGE, United Kingdom and CAMBRIDGE, Mass., April 10, 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 announces that preclinical data from FS222, a potentially best-in-class tetravalent bispecific antibody targeting both CD137 and PD-L1 will be presented in a poster at the 2021 American Academy of Cancer Research (AACR) Annual Meeting, taking place virtually from April 10-15 and May 17-21. Poster #1864, entitled ‘FS222, a Tetravalent Bispecific Antibody Targeting CD137 and PD-L1, is Designed for Optimal CD137 Interactions Resulting in Potent T cell Activation Without Toxicity’ will be available via on-demand viewing starting today, April 10, at 8:30 a.m. ET.

FS222 targets PD-L1, the immune checkpoint protein that regulates the balance of activated T cells in the immune system and is overexpressed on many solid tumors and CD137, a co-stimulatory molecule from the tumor necrosis factor receptor superfamily (TNFRSF), which is widely known to be upregulated on tumor-reactive CD8+ T cells or “killer T cells”. Currently, only a minority of patients have a long-lasting response to monotherapies that block the PD-(L)1 pathway.

Neil Brewis, Chief Scientific Officer at F-star Therapeutics, said: “We are encouraged by the results of these latest preclinical studies of FS222, our tetravalent bispecific antibody targeting PD-L1 and CD137. This work further demonstrates that FS222’s tetravalent binding mechanism is the most efficient and effective format for bispecific antibodies. The early onset of activity and T cell proliferation gives us confidence that FS222 will allow for a wide range of treatment options.”

FS222 was designed to be a potent human CD137/PD-L1 tetravalent conditional agonist with a unique combination of high affinity PD-L1 binding, and moderate affinity, but with high avidity, binding to CD137 on activated T cells to result in optimal receptor clustering. Previously, FS222 has been shown to exhibit a favorable safety profile in preclinical safety studies.

Tetravalent binding by FS222 demonstrated optimal activity in multiple preclinical pharmacology studies, outperforming classic heterodimeric bispecific antibodies. These data showed that there was no evidence of a hook effect, or bell-shaped dose response curve, in vitro, and coupled with FS222’s favorable safety profile, presents a potentially broad and differentiated therapeutic window. A murine surrogate mAb2 for FS222 had peripheral immunopharmacology, as shown by CD8+ T cell proliferation, at high dose levels, mirroring the in vitro data, whereby the tetravalent FS222 surrogate mAb2 outperforms other lower valency formats.

In January 2021, F-star announced that the first patient had been dosed in a Phase 1 clinical trial of FS222, a multicenter, open-label, first-in-human trial to evaluate the safety, tolerability, and early signs of efficacy of FS222 in adult patients diagnosed with advanced malignancies. The adaptive study design will allow for the early exploration of clinical activity of FS222 in a range of selected solid tumors that will guide future targeted clinical development.


About F-star Therapeutics, Inc.

F-star is a clinical-stage biopharmaceutical company developing tetravalent bispecific antibodies for a paradigm shift in cancer therapy. By developing medicines that seek to block tumor immune evasion, the Company’s goal is to offer patients greater and more durable benefits than current immuno-oncology treatments. Through its proprietary tetravalent, bispecific natural antibody (mAb²) format, F-star’s mission is to generate highly differentiated best-in-class drug candidates with monoclonal antibody-like manufacturability. For more information visit www.f-star.com and follow us on LinkedIn and Twitter.

Forward Looking Statements

Certain statements contained in this press release 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. 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 those discussed in F-star’s Annual Report on Form 10-K, as well as subsequent Quarterly Reports on Form 10-Q and other documents to be filed from time to time with the SEC. 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. 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

Shik.Helen10@gmail.com

EX-99.2

Exhibit 99.2

 

LOGO

FS222, a Tetravalent Bispecific Antibody Targeting CD137 and PD-L1, is Designed for Optimal CD137 Interactions Resulting in Potent T cell Activation Without Toxicity Matthew A Lakins, Jose Munoz-Olaya, Christel Veyssier, Daniel Jones, Emma Goodman, Quincy Kaka, Jennifer Ofoedu, Ryan Fiehler, Robert Hughes, Cristian Gradinaru, Daniel Gliddon, Michelle Morrow, Neil Brewis F-star Therapeutics Inc., Babraham Research Campus, Cambridge, UK Background Methods 2 2. FS222’s natural IgG1 architecture, tetravalency and highly 4. Tetravalent FS222 outperformed a heterodimeric bispecific antibody 6. Tetravalent FS222 surrogate mAb² provided optimal in CD137 (4-1BB, TNFRSF9) is expressed on activated lymphocytes, A CD137/PD-L1 bispecific mAb antibody (FS222) was generated tuned affinity resulted in ideal cell binding in multiple in vitro functional assays without hook effect + and its clustering leads to receptor agonism resulting in by introducing a bivalent affinity-optimised CD137-binding Fcab vitro activity and enhanced CD8 T cell proliferation in vivo lymphocyte proliferation and pro-inflammatory cytokine release. into a human IgG1 bivalent PD-L1 mAb. LALA mutations were First-generation CD137 antibodies for cancer therapy were high introduced to abrogate FcgR activity. To elucidate its mechanism + Primary CD8 T cell Activation Assay Human Primary MLR assay FS222 surrogate variant molecules were tested in a mouse primary T cell assay affinity and enabled for FcgR engagement with either severe of action, FS222’s binding valency was assessed by chemically- Tetravalent FS222 was tested against a A FS222 bound minimally to CD137 expressed by FS222 bound CD137 with avidity to cell lines CD8+ T cells + HEK.hPD-L1 cells CD4+ T cells + iDCs Mouse Primary OT-1 Assay toxicity or weak activity limiting their therapeutic benefit (Qi, X et crosslinked mass spectrometry mapping (XL/MS). Immune primary T cells, and required PD-L1 for optimal binding highly overexpressing CD137 20000 9000 heterodimeric bispecific antibody, which EC E 40000 + 50 max al. 2019). Next generation CD137 approaches remain a promising pharmacology models were also used to evaluate PD-L1 was monovalent for CD137 and PD-L1, CD8 T cells + OVA-pulsed B16-F10 cells (nM) (pg/mL) A Primary (activated) CD8+ T cell B Highly overexpressed cell line area for bispecific antibodies designed to redirect T cell activity to dependent FS222 agonism against variants with differing valency L) 15000 in multiple assays including: (~10,000 CD137 copies/cell): (~100,000 CD137 copies/cell) 6000 the tumor whilst limiting unwanted toxicities. We have rationally for each target. 6000 m 1) T cell activation assay where PD-L1 was 12000 g/ (pg/mL) 30000 0.02 28394 designed and developed a unique tetravalent bispecific antibody p ( 10000 utilized purely as a crosslinker and, FS222 g with natural architecture, targeting CD137 and PD-L1 through 5000 FS222 2 — 2) MLR where PD-L1 has both a functional CD137 Fcab I L L) CD137 Fcab 3000 8000 h hIFN highly tuned affinity, incorporating reduced FcgR binding for safe PD-L1 mAb 5000 consequence and acts as a crosslinker for g/m 4000 IgG Control ( p FI CD137 mAb 20000 and efficacious cancer therapy (Lakins et al. 2020). M MFI CD137 y - 3000 IgG Control N 0.04 16338 4000 0 0 m IF 0.001 0.01 0.1 1 10 0.001 0.01 0.1 1 10 100 PD-L1+ cell 2000 PD-L1 Antibody concentration (nM) Antibody concentration (nM) 10000 PD 1000 0 0.01 0.1 1 10 100 0.01 0.1 1 10 100 1000 Primary CD8+ T cell Activation Assay 0.5 31522 3000 Antibody Concentration (nM) Antibody Concentration (nM) CD8+ T cells + HEK.hPD-L1 cells Figure 2. 0 A Cell binding of FS222 to activated human primary CD8+ T cells that express both PD-L1 and CD137. L) 0.001 0.01 0.1 1 10 100 PD-L1 B Cell binding of FS222 DO11.10 cell line engineered to overexpress human CD137. 2000 Antibody Concentration (nM) Tetravalent Heterodimeric 5.1 28731 (pg/m versus FS222 bispecific bispecific B CD8+ T cell Proliferation - 2 FS222 3. FS222 tetravalency was demonstrated unequivocally using IL h 1000 20 ✱✱ crosslinking mass spectrometry mapping (XL/MS) CD137 CT26 1x105 implanted subcut into BALB/c a 0 Tetravalent FS222 outperforms 15 0.01 0.1 1 10 100 Single high dose of molecules to align with top A Principle of CovalX* XL/MS technique B Example of Mass Spectrum Antibody Concentration [nM] heterodimeric bispecific in + end of in vitro data L1 Figure 4. 10 2—L1 L1 Ki67 - L1 CD137 PD — A In vitro characterisation of FS222 in a primary CD8+ T cell activation assay, HEK cells engineered to multiple human primary Day 0 Day 7 Day 11    overexpress human PD-L1 immune cell assays with no % +    B In vitro characterisation of FS222 in a mixed lymphocyte reaction, using iDC and CD4 T cells from 5 Inoculation Single dose 4 days post-dose ity mismatched human PBMCs evidence of a hook effect blood sample T cell Intens C CD8+ T cell activation assay as in A, with an extended concentration curve to exemplify no hook    FS222 FS222+1CD137 FS222+1CD137+1CD137+1PD FS222+1CD137+2CD137+1PD FS222+1CD137+2CD137+2PD effect for tetravalent FS222 0 2 Figure 6. A In vitro characterisation of FS222 surrogate in primary OT-1 CD8+ T cell activation assay with cell-based crosslinking provided 1. By design, FS222 bound PD-L1 with high affinity and specifically interacted with CD13                5. Tetravalency resulted in full PDx blockade and optimal CD137 agonism by B16-F10 melanoma cells pulsed with OVA peptide and expressing PD-L1. Significance determined by Z test. n=3, grey                 circles: IgG control through highly tuned affinity to result in optimal receptor clustering in a human primary mixed lymphocyte reaction B CD8+ T cells from the blood of CT26 tumor bearing BALB/c mice were identified by CD3+/CD8+ staining and analysed for Ki67 expression on day 4 post dose. Data from 6 mice per group are shown with the line representing the mean. Significance determined by student’s t-test *, P < 0.05, grey circles: IgG control A FS222 Affinity to Monomeric Antigen B FS222 Avidity to Dimeric Antigen Molecules, based on FS222, were created with different valency to each EC E (hCD137-his) (hCD137-mFc) target were tested in an MLR assay 50 max (nM) (pg/mL) 40 K ~0.5 µM 2000 nM 40 K 0.66 nM D D Human Primary MLR assay 666.6 nM 27 nM 3000 Conclusion CD4+ T cells + iDCs 30 9 nM 30 222.2 nM 0.03 2062 U) 3 nM (RU) 74.1 nM (R 2500 FS222 was designed to be a potent human anti-CD137/PD-L1 tetravalent conditional 20 20 C FS222 bound tetravalently when CD137 1 nM e nse 24.7 nM agonist with a unique combination of high affinity PD-L1 binding, and moderate affinity pons 0.33 nM was in excess over PD-L1 10 8.2 nM s 10 with high avidity binding to CD137 on activated T cells. Previously, FS222 has been shown espo Re 0.11 nM 2000 R 2.7 nM 0.03 1428 0 L) m to exhibit a favourable safety profile with immunopharmacology in non-human primate 0 0 200 400 600 800 FS222’s natural structure presents an / g safety studies. -50 0 50 100 p ( 1500 Time (s) -10 Time (s) opportunity to bind each target y -10 N—Tetravalent binding by FS222 was required for optimal activity in multiple preclinical bivalently and simultaneously. F I 1.13 2283 D FS222 Affinity to Monomeric PD-L1 Antigen In a dynamic equilibrium system, h 1000 pharmacology studies, outperforming classical heterodimeric bispecific antibodies. There (hPD-L1-his) FS222 bound CD137 and PD-L1 was no evidence of a hook effect in vitro, and coupled with FS222’s favourable safety profile, presents a potentially very broad therapeutic window. FS222 surrogate mAb2 had 80 Figure 1. K 0.19 nM 81 nM antigens tetravalently. 500 + D peripheral immunopharmacology, as shown by CD8 T cell proliferation, at high dose A Surface plasmon resonance (SPR) showing FS222 affinity to 5.05 2404 60 27 nM monomeric hCD137-his. KD was determined using a 1:1 binding levels, mirroring the in vitro data whereby tetravalent FS222 surrogate outperforms model. Dashed lines show fitted curves. (RU) 9 nM Figure 3. 0 lower valency formats. 40 B SPR showing FS222 avid binding to dimeric hCD137-mFc. K e s D 0.001 0.01 0.1 1 10 100 3 nM A Lysine based BS3 crosslinkers were used to stabilize complexes that were then amenable to High MALDI-TOF analysis. Figure 5. n was estimated using a 1:1 binding model. Dashed lines show Antibody Concentration (nM) In many tumor settings, checkpoint inhibitors only provide moderate clinical benefit, and po 20 Resulting MS spectra peak intensity was then used to estimate the relative amount of protein and complexes present. FS222 activity in a human primary MLR assay against 1 nM fitted curves. B Mass Spectrum showing FS222 and FS222 complexes with antigens when CD137 was in excess before cross-linking completion C SPR showing FS222 affinity to monomeric hPD-L1-his. K was valency-variants of the same molecule. Green; tetravalent for many of those patients there is a strong mechanistic rationale for clinical outcomes to Res D 0 0.33 nM C Demonstration of FS222 tetravalency. Experiments were conducted by titrating in CD137 and PD-L1 antigen and relative Mass (FS222) bivalent for both targets. Red; bivalent for PD-L1, determined using 1:1 binding model. Dashed lines show fitted Spectrometry intensities of each complex species were plotted as relative percentages. Pie chart clearly shows FS222 has the A tetravalent bispecific antibody is the most efficient be improved with FS222 administration. We believe FS222 presents a unique opportunity, 0 200 400 600 800 curves. monovalent for CD137. Blue; monovalent for PD-L1, 0.11 nM versus high affinity and/or low valency CD137 binding bispecific molecules, by opening up -20 capability to bind CD137 and PD-L1 targets antigens tetravalently. way to induce receptor clustering and activation bivalent for CD137. Purple; monovalent for PD-L1 and Time (s) *With thanks to COVALX: www.covalx.com, Bich, C et al. (2010) Anal Chem. DOI: 10.1021/ac901651r monovalent for CD137. Grey; IgG control a broad therapeutic window. AACR Virtual Annual Meeting 2021    |    09 – 14 April    |    Poster Number: 2384 Qi, X., Li, F., Wu, Y. et al. (2019) Nat Comm 10, 2141 DOI: 10.1038/s41467-019-10088-1 Lakins et al. (2020). Clin Cancer Res April 28 2020 DOI: 10.1158/1078-0432.CCR-19-2958