#1BIOND BIOLOGICS ILT2 HLA-G ILT2 HLA-G ILT2 NK cells CDB T cells Suppressed Lymphocytes Suppressed Macrophage BND-22 BND-22 CD8 T CD80 Tumor BND-22 Activated Lymphocytes SCD28 Tumor BND-22 CD28 CD86 Anergic T cells T cell APC MMPs Corporate Presentation May 2021 for Anti-tumor activity BND-35 Activated myeloid cells Chemical ILT3 Activ Carier#2Company Overview About Us Biond Biologics is a private clinical-stage biopharmaceutical company, developing novel immunotherapies for cancer and a platform enabling the intracellular delivery of biologics . • Our Innovation At the forefront of research of immune-evasion mechanisms and its translation into novel cancer therapeutics Advanced in-house research capabilities and access to fresh tumor and blood samples from cancer patients A Transformative platform enabling delivery of biologics into cells, targeting intracellular "undruggable" proteins The Team • Proven track record for developing novel drug candidates from scientific concept to clinical trials • Highly experienced in fund raising - securing private and public funding Successfully partnering with large biopharma companies: . . July 2015- Merck/CCAM; CM-24 mAb, phase-1 asset (M&A, $95M upfront) ⚫ Jan 2021- Sanofi/Biond; BND- 22 mAb, IND ready asset (Licensed, $125M upfront) BIOND BIOLOGICS Biond Biologics Corporate Presentation | May 2021 | Non-confidential 2#3BIOND BIOLOGICS Financial highlights (三) ISRAEL BIOTECH FUND FINANCING PARTNERSHIP WITH SANOFI SANOFI $21M in equity financing since launch HAREL SBIJI Bristol-Myers Squibb Insurance & Finance $125M upfront payment ⚫ In January 2021 Biond signed a licensing agreement with Sanofi for BND-22 • Terms: $125M upfront payment and over $1B in development, regulatory, and sales milestones, as well as tiered double digit royalty payments ⚫ Biond is leading the BND-22 phase 1 study for safety and tolerability as a single agent and combination. ⚫ Sanofi will continue clinical development and commercialization responsibilities thereafter Biond Biologics Corporate Presentation | May 2021 | Non-confidential 3#4BIOND BIOLOGICS Experienced leadership Tehila Ben Moshe, PhD CEO CCAM PROTALIXX Biotherapeutics Biotherapeutics Ori Shilo, MBA CFO Red Hill Biopharma ProSeed Capital Holdings CVA Avidor Shulman, PhD VP R&D PROTALIXX Biotherapeutics Itay Friedman, MD VP Clinical Development Bristol-Myers Squibb Biond Biologics Corporate Presentation | May 2021 | Non-confidential Yair Sapir, PhD COO CCAM Biotherapeutics 4#5BIOND BIOLOGICS Advisory Boards Board of Directors • Tehila Ben Moshe, PhD CEO, Biond Biologics Ori Shilo, MBA CFO, Biond Biologics ⚫ Yuval Cabilly, PhD Co-founder and managing Partner, Israel Biotech Fund ⚫ Ronit Bendori, PhD General Partner, Evergreen • Tomer Goldberg VP, Managing Director, Harel Insurance & Finance . Jerry Zeldis, MD, PhD Former Chief Medical Officer, Celgene Scientific Advisory Board • Alan Korman, PhD Former VP Immuno-Oncology Discovery at BMS Bristol-Myers Squibb . Jeffrey Weber, MD, PhD Deputy Director, Perlmutter Cancer Center, NYU Langone Medical Center ⚫ Pavel Pisa, MD, PhD Former Head of Translational Medicine at Roche Gal Markel, MD, PhD Deputy Director General, Rabin Medical Center NYU Langone MEDICAL CENTER Roche RABIN MEDICAL CENTER BEILINSON - HASHARON Biond Biologics Corporate Presentation | May 2021 | Non-confidential 5#6BIOND BIOLOGICS Pipeline of first-in-class drug candidates Program Immuno-Oncology BND-22: ILT2 (LILRB1) anti-ILT2 blocking mAb BION-206: Soluble CD28 reduction Overcoming anti-PD-1 resistance by targeting CD28 shedding BND-35: ILT3 (LILRB4) anti-ILT3 blocking mAb INspire - Intracellular Delivery Platform BION-301: Intracellular Oncology Target Biologic agent targeting oncogenic cell signaling regulator Discovery Pre-Clinical Development IND enabling Studies Phase 1 Phase 1 on-going Biond Biologics Corporate Presentation | May 2021 | Non-confidential 6#7BIOND BIOLOGICS Immuno-oncology pipeline and intracellular delivery platform BND-35 TAM/DC/ MDSC BND-22 BND-35 TAM: DC: Tumor-associated macrophages Dendritic cells MDSC: Myeloid derived suppressor cells APC: NK: Antigen presenting cells Natural killer BND-22 APC BION-206BND-22 T/NK Cell Tumor Cell Biond Biologics Corporate Presentation | May 2021 | Non-confidential INspire platform 7#8ILT2 NK cells Inhibitory Signal CD8 T cells EMRA BND-22 HLA-G Inhibitory Signal ILT2 Tumor HLA-G ILT2 Tumor Suppressed Lymphocytes Don't Eat Me" Signal Suppressed Macrophage BND-22 Tumor BND-22 Tumor BND-22 احمد NK cells CD8 TEMRA cells Activated Lymphocytes Activated Macrophage BND-22 ILT2 Blocking Antibody Biond Biologics Corporate Presentation | May 2021 | Non-confidential BIOND BIOLOGICS 00 8#9BIOND BIOLOGICS ILT2: a multi-cell inhibitory immune checkpoint, on innate and adaptive immune cells An inhibitory immunomodulatory receptor (aka LILRB1, CD85j) Ig domains ITIMS ILT2 Receptor Expressed on multiple immune cell types: Lymphoid cells (T cells, NK cells), Myeloid cells (macrophages). Binds with the highest affinity to human leukocyte antigen (HLA)-G, a known immunosuppressive molecule expressed by multiple tumor types Generates inhibitory signals via ITIM-mediated recruitment of SHP- 1, resulting in potent inhibition of immune effector functions when bound by MHC ligands Extracellular lg-like domains bind to classical and non- classical MHC-I molecules ILT2, Ig-like transcript 2; IgSF, Immunoglobulin superfamily; ITIM, Intracellular tyrosine-based inhibitory motifs; SHP1, Src homology region 2 domain-containing phosphatase 1; MHC, Major histocompatibility complex; HLA, Human leukocyte antigen Biond Biologics Corporate Presentation | May 2021 | Non-confidential 9#10BND-22 is an antagonist antibody that blocks ILT2, on innate and adaptive immune cells BND-22 enhances the ability of macrophages to phagocytose tumor cells BND-22 enhances anti-tumor activity of T cells and NK cells HLA-G "Don't Eat Me" Signal ILT2 Tumor Suppressed Macrophage BND-22 Tumor BND-22 ILT2 NK cells Inhibitory Signal CD8 T cells EMRA BND-22 HLA-G Activated Macrophage Inhibitory Signal ILT2 Tumor Suppressed Lymphocytes Tumor BND-22 BND-22 is a humanized IgG4 antibody that enhances the anti-tumor activity of immune cells by blocking ILT2 from binding to HLA-G and MHC-I TEMRA, effector memory T cells re-expressing CD45RA BIOND BIOLOGICS Biond Biologics Corporate Presentation | May 2021 | Non-confidential NK cells CD8 T cells EMRA Activated Lymphocytes 10#11BIOND BIOLOGICS BND-22 enhances anti-tumor activity in-vivo Melanoma lung lesion + PBMC Tumor cells (MEL526) SCID-NOD mice S ↑ Abs IV ↑↑ PBMC IV 0 5 10 15 20 25 ↑ ↑ Lung metastasis evaluation 50 Tumor only Donor 1 Donor 2 Donor 3 PBMC + IgG PBMC + BND-22 Naïve Tumor weight (mg) 500 TGI = 58% 400- 300 200 100 SC colon cancer+ macrophages Tumor cells (COLO-320) NSG 03 7 10 Monitor tumor growth mice Macrophages Abs ↑sc Tiv Tiv Tiv Tumor vo,ume (mmĂ) 1000 500 Mo + control IgG 20 25 30 35 Days Tumor vo,ume (mmĂ) 1000 500 T Mo + BND-22 TGI = 91% 20 25 30 35 Days Tumor weight was calculated by subtracting naïve mice lung weight form the lung weight of the different mice. TGI - tumor growth inhibition. 涯 Isotype BND-22 *P<0.05, Student's T test compared to control IgG. N = 5-9 mice for each group. control Biond Biologics Corporate Presentation | May 2021 | Non-confidential 11#12BND-22 development plan: potential initial efficacy signals by mid-2023 2020 2021 2022 2023 2024 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 IND BND-22 Monotherapy BND-22 Monotherapy BND-22 + Cetuximab BND-22 + anti-PD-1 Dose Escalation 8 sites; US and Israel Dose Expansion 15-20 sites; US, EU and Israel IND, Investigational New Drug; FPI, First Patient In BND-22 + Cetuximab BND-22 + anti-PD-1 BIOND BIOLOGICS Biond Biologics Corporate Presentation | May 2021 | Non-confidential 12#13BIOND BIOLOGICS BND-22 Target Product Profile Product Description E Scientific Rationale MOA/Clinical Pharmacology • • Ig-Like Transcript 2 (ILT2) blocking antibody Strategic Context / Differentiation Novel multi-cell checkpoint inhibitor enhancing the anti-tumor activity of both the innate and adaptive immune systems with the potential to overcome PD-1 resistance Preclinical data support combination with cetuximab, and PD-1 blockers • Binding of MHC-I molecules to the ILT2 receptor expressed by macrophages, T-cells and NK cells inhibits anti-tumor effector functions of these cells Upregulation of ILT2 ligands, (E.g., HLA-G) occurs in multiple tumor types and is associated with poor prognosis Indication(s) and patient 3 population HLA-G-expressing solid tumors Patients with unrespectable or metastatic disease, with disease progression following prior systemic therapies BND-22 is an antibody that binds to the ILT2 receptor and blocks its interaction with MHC-I molecules Releases ILT2 pathway-mediated inhibition of the innate and adaptive anti-tumor immune response Blocking ILT2 activity enhanced macrophage phagocytosis and NK and T cells cytotoxicity activity against cancer cells Extensive biomarker/ PD marker strategy in place # Stage Biond Biologics and Sanofi enter into global licensing agreement Q3 2020 Phase I initiated Q1 2021 Biond Biologics Corporate Presentation | May 2021 | Non-confidential 13#14BND-22: Summary (OPTIONAL) Using In-house research capabilities BND-22 was developed from scientific concept to clinical trials First-in-human, phase 1 study, Initiated in Q1 2021 (single agent and combination with approved therapeutics) A humanized IgG4 antibody that enhances the anti- tumor activity of immune cells by blocking ILT2 from binding to HLA-G and MHC-I BND-22 was licensed to Sanofi with upfront payment of $125M, over $1B in milestones and royalty payments BIOND BIOLOGICS Biond Biologics Corporate Presentation | May 2021 | Non-confidential 14#15CD80 sCD28 CD28 CD86 Anergic T cells T cell APC MMPS BION-206 Targeting CD28 Shedding BIOND BIOLOGICS 15#16CD28 pathway's central role is validated by current approved immunotherapies CTLA-4 regulatory pathway: Competition on CD80/86 binding BIOND BIOLOGICS CD80/CD86 CD28 APC CTLA-4 (higher affinity to CD80/86 molecules) T cell inhibition Anti-CTLA4 blocking antibody Approved in melanoma and RCC PD-1 regulatory pathway: suppression by dephosphorylation of CD28 CD80/CD86 PD-L1 CD28 PD-1 SHP-2 T cell inhibition Biond Biologics Corporate Presentation | May 2021 | Non-confidential APC Anti-PD1 blocking antibody Approved in multiple tumor types e.g., melanoma, lung, RCC, H&N, HCC, bladder 16#17Model for the immuno-suppressive effect of CD28 shedding Stimulation of T cells CD28 shedding from activated T cells CD80 CD86 T cell APC Pro-MMPs sCD28 CD28 MMPs sCD28 T cell sCD28 serves as a decoy receptor CD80 CD86 sCD28 CD28 T cell APC MMPs BIOND BIOLOGICS Activated T cell During the stimulation of T cells, Matrix Metalloproteinases (MMPs) are upregulated and cleave CD28 at its stalk region, releasing a dimeric soluble CD28. Anergic T cells SCD28 acts as a decoy receptor by binding to CD28 cognate ligands, CD80 and CD86 on antigen presenting cells (APC). Activated T cells with lower membranal CD28 density and insufficient B7 mediated signaling become anergic and cannot generate proper immune response against malignant cells. Biond Biologics Corporate Presentation | May 2021 | Non-confidential 17#18BIOND BIOLOGICS Soluble CD28 protein in plasma (pg/mL) CD28 shedding is a novel immune regulatory pathway in cancer patients The BION-206 program is based on novel Biond discoveries: Aberrant levels of soluble CD28 were found in cancer patients' plasma (WO 2019/175885) The CD28 receptor was found to be cleaved from activated T cells by cancer related MMP's (PCT/IL2020/051243) Soluble CD28 promotes an immuno-suppressive environment 50000 100000 • Above 1 μg/ml NR Melanoma Pancreas Head & Neck Lung Bladder Breast Colorectal Gastric Ovarian Kidney Sarcoma . 11 tumor types were surveyed 15% of samples of studied tumors plasma contain a higher level of soluble CD28 compared to plasma from healthy subjects MMP, matrix metalloproteinases Biond Biologics Corporate Presentation | May 2021 | Non-confidential 18 涯#19Soluble CD28 attenuates anti-PD-1 effect in cancer PD-1 therapy is uniquely sensitive to CD28-B7 axis activation (T-cell - APCs) CD80/CD86 APC PD-L1 CD28 鱼 PD-1 SHP-2 T cell IFNg (pg/mL) sCD28 (pg/mL) 25000 20000 15000 10000 5000 Soluble CD28 attenuates anti-PD-1 effect in cancer PBMC ○ Naive SEB SEB + CD28 SEB + SEB + Keytruda Keytruda + SCD28 H&N Cancer donor #9 * P<0.05, unpaired student T.test Compared to MK3475 treatment Soluble CD28 dynamics relates with response to PD-1 pathway therapy 12000 CR PD 8000 4000 ○ IFNg (pg/mL) 16000 PR PD 12000 8000 4000 0 BIOND BIOLOGICS Activation inhibition Kamphorst AO, Science, 2017; Hui E, Science, 2017 16 18 26 30 34 37 41 45 48 42 46 50 54 58 62 Time from first dosage of anti-PD1 therapy (weeks) Urothelial carcinoma donor treated with Nivolumab 0126 10 13 15 19 22 26 28 33 35 39 Time from first dosage of anti-PD1 therapy (weeks) Melanoma donor treated with Nivolumab CR- Complete response: PR - Partial response,: PD - progressive disease Biond Biologics Corporate Presentation | May 2021 | Non-confidential 19 涯#20Lead BION-206 agent is in pre-clinical development A lead clone has been isolated and characterized for: Specific binding to CD28 proteolytic site Clean safety profile - no agonistic or antagonistic activity Prevents receptor shedding in various immune assays OD (450nm) BIOND BIOLOGICS 5. 4 3 0.01 0.1 1 BION-206 (μg/ml) CD28 Targeted shedding site T cell In-vitro blocking CD28 cleavage by MMP-2 1.2 n-cells CD28-shedding blocking activity 5000 1 0.8 0.6 0.4 0.2 0 10 Peptide MMP-2 0.024 0.12 0.6 MMP-2 + BION 206 (μM) 4000- 3000 2000 1000 Biond Biologics Corporate Presentation | May 2021 | Non-confidential H No Stim. SEB SEB+ TMI-1 0,024 0.12 0.6 3 SEB + BION 206 (μM) 涯 20 20#21BION-206 is a first-in-class immuno-oncology agent targeting the CD28/B7 axis Protection of CD28 shedding by BION-206 CD80 CD28 BION-206 CD86 APC T cell MMPs BIOND BIOLOGICS Activated T cells Lowers soluble CD28 levels thus preventing its immunosuppressive effect Restores CD28 signaling in T cells Enables efficient stimulation of T cells in lymph nodes and the TME Enhances the effect of PD1 blockade Biond Biologics Corporate Presentation | May 2021 | Non-confidential 涯 21 24#22BIOND BIOLOGICS BION-206 Program Gannt MOA studies (In Vivo, Ex Vivo) Lead development (affinity maturation, engineering, Humanization) CMC + GMP production IND enabling studies (TOX, TCR, In vitro safety PK, ADA, etc...) Regulatory filing (Pre-IND, IND) Phase 1 2021 2022 2023 2024 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Pre IND IND Biond Biologics Corporate Presentation | May 2021 | Non-confidential 22#23BION-206 Target Product Profile 自 Product Description Antibody fragment targeting the CD28 receptor BIOND BIOLOGICS {! . Scientific Rationale MOA/Clinical Pharmacology CD28 receptor is shed from activated T cells. The soluble forms serve as a decoy receptor and were found in the serum of cancer patients Soluble CD28 was found to inhibit T cells activity, and attenuate the activation signal of anti-PD-1 blockade The identified CD28-cleaving MMPs are known to be highly expressed in tumor tissues BION-206 binds to the shedding region of CD28 and sterically hinders access for MMPs BION-206 is designed to augment T cells activation, particularly memory T cells Strategic Context / Differentiation Indication(s) and patient 3 population • • A novel regulatory mechanism in the CD28/B7 axis (1st in class) Has the potential to overcome PD-1 resistance • Solid tumors with immune infiltration in patients with unresectable or metastatic disease, including anti-PD1 refractory patients # Stage Pre-clinic Biond Biologics Corporate Presentation | May 2021 | Non-confidential श्र 23#24BION-206: Summary OPTIONAL A novel regulatory mechanism discovered by Biond in the CD28/B7 axis (1st in class) Lead BION-206 agent was selected and is under pre- clinical development BION-206 binds to the shedding region of CD28 and sterically hinders cleavage resulting in augment T cells activation Targets solid tumors with immune infiltration in patients with unresectable or metastatic disease, including anti-PD1 refractory patients BIOND BIOLOGICS Biond Biologics Corporate Presentation | May 2021 | Non-confidential 24 24#25Tumor Anti-tumor activity BND-35 Activated myeloid cells ILT3 Activated T cell BND-35 ILT3 Blocking Antibody BIOND BIOLOGICS 25#26ILT3: a key protein driving suppressive myeloid cells activity in cancer Immunoglobulin-like transcript 3 (ILT3) is an inhibitory immune- receptor containing three ITIM sequences Can be found on suppressive myeloid cells in the TME: TAM, MDSC and DCtol Ig domains ooooooo00 0000000000000000 000 ITIMS ILT3 Receptor Exists in membranal and soluble forms which are both active Inhibits the effector activity of T cells and enhances the suppressive activity of myeloid cells Reported T cells ligands include APOE, ALCAM, PI16 BIOND BIOLOGICS ILT3, Ig-like transcript 3; ITIM, Intracellular tyrosine-based inhibitory motifs; TAM, Tumor-associated macrophages, MDSC, Myeloid-derived suppressor cells; Dctol, Tolerogenic dendritic cells; Biond Biologics Corporate Presentation | May 2021 | Non-confidential 26#27BND-35 is an antagonist antibody that blocks ILT3 BND-35 promotes an inflammatory TME Suppressive tumor microenvironment Decreases activity of suppressive myeloid cells Increases effector T cell activity Inflammatory tumor microenvironment Tumor Pro-tumorigenic signals ILT3 Inhibitory Signal BND-35 Tumor Anti-tumor activity BND-35 BIOND BIOLOGICS Suppressive myeloid cells Suppressed T cell Activated myeloid cells Biond Biologics Corporate Presentation | May 2021 | Non-confidential ILT3 Activated T cell 27 27#28ILT3 is highly prevalent in myeloid cells in the tumor microenvironment of different cancer types IHC staining of ILT3 (red staining) and CD68 (blue staining) ILT3 levels in various cancers (IHC) Breast cancer Kidney cancer H&N cancer Lung cancer 100 90 Sarcoma Stomach cancer Ovarian cancer % cases positive for ILT3 2000 70 60 50 40 30 20 10 80 Breast cancer Kidney H&N Lung Sarcoma Gastric Ovarian cancer cancer cancer cancer cancer BIOND BIOLOGICS Arrows point to double- positive cells Cases were considered Target -positive if >200 ILT3+ cells were detected Biond Biologics Corporate Presentation | May 2021 | Non-confidential 28#29BND-35 restores T cell activity inhibited by various suppressive myeloid cells IFNg (pg/ml) DCtol + CD4 T cells 25,000 I 20,000 15,000 10.000 5,000 ○ iDC+CD4 T cells H Control IgG BND-35 DCtol + CD4 T cells BIOND BIOLOGICS DCtol, tolerogenic dendritic cells; MDSC, myeloid-derived suppressor cells Anti-tumor activity IFNg (pg/ml) BND-35 30,000 25,000 20,000 15,000 10.000 5,000 MDSC + CD8 T cells * H MDSCs naïve activated Medium control BND-35 T cell CD8 T cell IgG Controls CD8 T cells + MDSCs ILT3 Activated T cell * P<0.05; un-paired Student's T-test compared to control IgG Activated myeloid cells Biond Biologics Corporate Presentation | May 2021 | Non-confidential 涯 29 29#30BIOND BIOLOGICS BND-35 Program Gannt 2021 2022 2023 2024 MOA studies (In Vivo, Ex Vivo) Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Lead Humanization CMC + GMP production IND enabling studies (TOX, TCR, In vitro safety PK, ADA, etc...) 7 Regulatory filing (Pre-IND, IND) Phase 1 Pre IND IND Biond Biologics Corporate Presentation | May 2021 | Non-confidential 30#31BIOND BIOLOGICS • ° BND-35 Target Product Profile Product Description Ig-Like Transcript 3 (ILT3) receptor antagonist antibody Strategic Context / Differentiation Checkpoint inhibitor targeting immuno- supresisve cells in the TME ILT3 is a new, emerging target in cancer immunotherapy }: Scientific Rationale Suppressive myeloid cells in the tumor microenvironment (TME) limit the potency of therapeutic interventions ILT3 is expressed by suppressive myeloid cells in cancer patients and has a key role in the activity of these cells ILT3 inhibits the effector activity of T cells and enhances the suppressive activity of myeloid cells MOA/Clinical Pharmacology BND-35 is an antibody that binds to the ILT3 receptor and disrupts its interaction with its T cell ligand, Releases ILT3 mediated immuno-supression in the TME to enable efficient anti-tumor immune activity Indication(s) and patient 3 population • Solid tumors known to have a highly suppressive tumor microenvironment 目 # Stage Pre-clinic Patients with unresectable or metastatic disease, with disease progression following prior systemic therapies including PD(L)-1 blockers Biond Biologics Corporate Presentation | May 2021 | Non-confidential 31#32BND-35: Summary BIOND BIOLOGICS C. ? ? ? Biond Biologics Corporate Presentation | May 2021 | Non-confidential 32 32#33Antibody Payload Carrier Chemical Modifications १९ INspire Biologics Intracellular Delivery Platform BIOND BIOLOGICS#34Platform enabling intracellular delivery of biologics Biond's INspire intracellular delivery platform is based on scalable chemical modifications applied to a carrier that enable: Cell membrane- crossing by exploiting natural endocytosis Chemical Modifications Antibody Payload Carrier 2 1 5 ११ 3 Efficient endosomal escape Cytoplasm dispersibility BIOND BIOLOGICS Biond Biologics Corporate Presentation | May 2021 | Non-confidential 4 34 34#35INspire: Endosomal escape, cytoplasmic dispersibility and target binding of internalized antibody Anti-Vimentin Antibody (cytoskeletal protein) successfully delivered, released, and bound to its target inside cancer cells Anti-Ab (Red) Nuclear Stain (Blue) Anti-Vimentin (Green) Nuclear Stain (Blue) Anti-Ab (Red) Anti-Vimentin (Green) Nuclear Stain (Blue) Antibody Payload Anti- Vimentin Carrier Chemical Modifications Anti-Ab. 647 (green) : Nuclear Stain (blue) BIOND BIOLOGICS Biond Biologics Corporate Presentation | May 2021 | Non-confidential 35 55#36INspire: Intracellular delivery of anti mutated K-RAS protein (in-vitro PoC) Anti-K-RASG12V protein internalized into lung adenocarcinoma cells and localizes to K-RAS sites (inner-side of cell membrane) Effect of intracellularly delivered anti-K-RAS protein agent on apoptosis of KRASG12D pancreatic ductal carcinoma cell line Apoptosis (Annexin V staining) 30000 25000 20000 15000 10000 5000 Chemical Modifications Antibody Payload HA 20 40 60 80 100 Time (hr) Annexin V staining - A common method for detecting apoptotic ("dying") cells BIOND BIOLOGICS Carrier Biond Biologics Corporate Presentation | May 2021 | Non-confidential 36#37BIOND BIOLOGICS INspire: Intracellular delivery of anti-HPV-E7 (In-vitro PoC #2) HPV-E7 is an oncoprotein that activates cell cycle (and cell proliferation). Intracellular delivery of an anti-HPV- E7 protein agent led to cell cycle arrest and killing of HPV18-E7+ cervical cancer cells 100 Positive Control (CDK 4/6 Inhibitor) E2 integrated HPV E2 Genomic DNA E7- E7 + Gene Transcription E2F transcription factor (Rb-bound) Rb E2F (unbound) E7 Rb DNA cell cycle activation; proliferation Antibody Payload Anti-E7 Carrier Cell Cycle Arrest (%) EN WB 2 g 70 Chemical Modifications 0 60 88 80 Anti-E7-Carrier Negative Controls 100 120 140 160 Time (hr) Biond Biologics Corporate Presentation | May 2021 | Non-confidential 涯 37#38BIOND BIOLOGICS INspire Target Product Profile Technology Description Therapeutic binding agents able to block or activate intracellular targets and pathways The agents are chemically linked to a proprietary chemically modified carrier enabling the transport of the agent inside cells • . E Scientific Rationale Biologic agents, e.g. antibodies, cannot enter cells Many cancer and other diseases are caused by abnormal intracellular proteins, protein-protein interactions or pathways which are deemed undruggable due to the requirement of interference by a biologic agent The INspire agents can effectively address these undruggable targets and yield novel therapies MOA/Clinical Pharmacology The ability to target intracellular targets with biologic agents enables to address targets that cannot be addressed with small molecules and exploits their selectivity and high affinity to avoid off-target effects Strategic Context / Differentiation • Novel technology inspired therapeutic agents with unique MOAS • ☑ Indication(s) and patient population The INspire agents can be used to address multiple diseases and conditions The first INspire product will address HPV-E7 cancers where there is still unmet need and very clear patient selection criteria 目 ㅍ Stage Successful in vitro proofs of concept (HPV+ and KRAS cancers) PK and biodistribution successful PoC In vivo proof of concept studies are ongoing Biond Biologics Corporate Presentation | May 2021 | Non-confidential 38#39BION-300: Summary and next steps Carrier platform enabling intracellular delivery of biologics targeting "undruggable" proteins In vitro, proof-of- concept studies have demonstrated: antibody internalization endosomal escape cytoplasm dispersibility functional target binding Preliminary in vivo studies have demonstrated efficient pharmacokinetics and biodistribution BIOND BIOLOGICS Biond Biologics Corporate Presentation | May 2021 | Non-confidential 39#40Thank You Tehila Ben-Moshe [email protected] Ori Shilo [email protected] BIOND BIOLOGICS 40