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Annual Healthcare Conference 1 `
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BioAtla is a clinical-stage biotech company focused on
transforming cancer therapy with Conditionally Active Biologics (CABs) THE COMPANY TECHNOLOGY CLINICAL & TEAM FINANCE & INFRASTRUCTURE Proprietary CAB technology that Broad clinical and development Building on successful 2020 IPO,
conditionally and reversibly bind to pipeline with two 1st-in-class P2 over $290MM in gross proceeds, cancer cells, but not to normal CAB-ADCs for multiple indications (including $75.0 MM raised 9/21). cells, enabling increased antibody and
CAB-CTLA-4 initiated P1 clinical $245MM cash at EOY 2021 funds potency and reduced toxicity studies operations into 2024 Strong intellectual property rights: Headquartered in San Diego in a - 621 patents (360 issued, 9 Over 60 employees with
exceptional ~43,000 square foot office and lab allowed, and 252 pending) experience in innovative research facility with a contract lab in and clinical development Beijing 3
Tumor cell acidity enables selective, reversible CAB binding via the
novel TM* physiological-occurring PaCS molecule mechanism THE TECHNOLOGY In Acidic Cancer Cell Membranes In Alkaline Healthy Cell Membranes BioAtla CAB antibodies In normal tissue (+) charged In the acidic TME the PaCS selectively target
these (+) 1 amino acid residues shield 3 molecules are neutralized protein targets from drug by H+, exposing targets to charged amino acids on The Warburg Effect attack by binding to (-) drug attack. With no targets only available in the TM charged
PaCS molecules. requirement for activation. acidic TME. Cancer cells divide rapidly, 2 requiring high rates of glycolysis**, resulting in an acidic TME (pH 5.8-6.7). + H + H + H Binding + H + H + H + H + H TM *PaCS = Protein-associated Chemical
Switches **Glycolysis underpins the success of PET scanning 4 Prodrugs and masked antibodies require activation. Once activated, they cannot become inactive circulating from diseased to normal tissues. Chang, H.W., Frey, G., Liu, H., Xing, C.,
Steinman, L, Boyle, B.J., & Short, J.M. (2021) PNAS 118(9): 1-10, Suppl. 1-19..
Leveraging advantages of CAB technology Anticipated advantages of CAB
technology Examples of CAB technology's broad application Improved safety and efficacy Targeting CTLA4 1 (BA3071 - Naked Antibody) Enhanced pharmacologic properties Targeting EpCAM x CD3 2 (BA3182 - Bispecific) Develop therapeutics
against validated pathways Targeting Nectin-4 3 Expand target universe nd (BA3361 - 2 Gen ADC ) 2nd Gen ADC features complementing CAB Technology: Enable differentiated combination and 1. conjugation without sequence modification
of antibody at DAR 4 and higher bispecific immuno-oncology therapies 2. high serum stability and high solubility with sugar-based linker 3. cleavage only in the lysosome with potential to reduce risk of neutropenia and neuropathy 5
BA3071 (CAB-CTLA4): best-in-class and potential for disruption of the
I/O Market Nivolumimab Nivolumimab (PD-1) + Research demonstrates challenges and Clinical Endpoint (PD-1) Ipilumimab (CTLA4) opportunity in combining two Immune Progression Free Survival 6.9 months 11.5 months Checkpoint Inhibitors* Grade 3 or 4
Adverse 16.3% 55.0% Improves efficacy, but increases adverse events Events Greater % of patients discontinue therapy relative Discontinued Treatment 7.7% 36.4% to monotherapy Vehicle Control In NHP study, BA3071 achieved similar Nivo
+ Ipi exposure levels to Ipi analog with significantly Positive Control less toxicity in combination with nivo** Nivo + CAB- GI Symptoms BA3071 Liquid feces Non-formed feces Other GI symptoms *Larkin et al., New Eng. J. Med.,373: 23-34, 2015 **Chang
et al., PNAS 118 (9): 1-10, 2021 Nivo: 20mg/kg QW (12X human dose); Ipi or CAB-CTLA: 15mg/kg QW (45 - 60X human dose) 6 Once weekly for four weeks exposure to Nivo + Ipi or CAB CTLA4
CAB-EpCAM x CAB-CD3 bispecific antibody exhibits comparable tumor
shrinkage with superior safety profile CAB EpCAM x CAB CD3 bispecific Dual selection results in high selectivity demonstrates efficient tumor shrinkage Tumor Cell Target CAB-EpCAM CAB-CD3 T Cell Target Bispecific Safety Results (Non-GLP; Non-human
Primates) MiXeno Model with HCT116 = Colorectal Cancer Cell Line WT-EpCAM x WT-CD3 1mg/kg twice/week in mice CAB-EpCAM x CAB-CD3 (BA3182) (equivalent to 0.25mg/kg in non-human primates) *0.25mg/kg = 2 normal *0.025mg/kg = 2 ill *1.0 mg/kg = 2 normal
*0.05 mg/kg = 2 expired *2.5 mg/kg = 2 normal *2.5 mg/kg = 10 normal *5.0 mg/kg = 10 normal >160x higher therapeutic index *Single Dose - non-GLP Toxicity Study *QW x 4 weeks - GLP Toxicity Study MTD not yet reached WT
= wild type; *from independent experiments MTD = Maximum Tolerated Dose 7 3 Tumor volume (mm )
Robust pipeline of differentiated CAB assets designed to deliver near-,
mid- and long-term value IND Enabling Phase 1 Phase 2 Program Target Lead Indications Pre-Clinical Clinical BA3011 STS & Bone Sarcoma NSCLC (Mono & Combo w/ PD-1) Mecbotamab Vedotin AXL Ovarian Cancer*
NSCLC BA3021 Melanoma (Mono & Combo w/ PD-1) ROR2 HNC Ozuriftamab Vedotin Ovarian Cancer* RCC Bladder BA3071 NSCLC / SCLC Gastric CTLA-4 HCC Cervical Cancer Naked Antibody
Melanoma (Mono & Combo w/ PD-1) Colorectal BA3182 Prostate Cancer** NSCLC / SCLC EpCAM & CD3 TNBC Bispecific Ovarian HNC Pancreatic BA3142 Melanoma Prostate
Cancer** B7-H3 & CD3 Bispecific NSCLC / SCLC Sarcoma Colorectal Cancer** BA3361 Pancreatic HNC Nectin-4 nd TNBC 2 Gen ADC NSCLC Breast BA3151 Ovary Colon B7-H4
nd Prostate 2 Gen ADC Kidney Bladder BA3311 Pancreatic Cancer** EGFR & CD3 Bispecific TNBC 8 * Ph2 investigator-initiated trial for Ovarian Cancer ** Anticipated indications based upon tumor target
expression Abbreviations: STS = Soft Tissue Sarcoma, NSCLC = Non-small Cell Lung Cancer, RCC = Renal Cell Carcinoma, SCLC = Small Cell Lung Cancer, HCC = Hepatocellular Carcinoma, TNBC = Triple-Negative Breast Cancer, HNC = Head and Neck Cancer
Strong execution and compounding momentum through 2021 2021 LOOKBACK
Initiated four Phase 2 Entered into clinical potentially collaboration with BMS to Secured $75m registration-enabling evaluate two CAB-ADCs in through private studies across two combination with Opdivo placement different assets
Mecbotamab Vedotin (AXL BA3011) Initiated CAB-CTLA4 Ozuriftamab Vedotin (ROR2 BA3021) Presented Phase 1 (BA3071) Phase 1 trial data in refractory sarcoma patients for Advanced two CAB- Mecbotamab Vedotin bispecific antibodies nd (BA3011) at
CTOS and two 2 Gen ADCs to IND enabling studies 9
Four potentially registration-enabling Phase 2 trials ongoing with lead
CAB-ADCs, Mecbotamab Vedotin & Ozuriftamab Vedotin Trial Status (Feb. 22) # PHASE 2 Sarcoma (STS & Bone) 26 sites activated Ongoing mono & combo w/ PD-1; AXL TmPS* 50 & 70 70 pts fully enrolled rd 3 Line
(n=200-275) Mecbo - BA3011 NSCLC 42 sites activated mono & combo w/ PD-1; AXL TmPS* 50 Actively dosing in PD-1, EGFR or ALK failure patients (n=40) Melanoma 16 sites activated Actively dosing mono & combination w/ PD-1; ROR2
positive ROR2 TmPS* 1; PD1 failure patients (n=200) Ozurif - BA3021 39 sites activated NSCLC Actively dosing mono & combination w/ PD-1; ROR2 positive ROR2 TmPS* 1; PD1, EGFR or ALK patients (n=200) Initiated Head & Neck
(SCCHN) Initial sites activated, mono & combination w/ PD-1 (n=80-100); ROR2 positive Ozurif - BA3021 dosing 1H 2022 ROR2 TmPS* 1; Platinum or PD-1 failure patients Ovarian (Investigator-Initiated Trial) Initial sites activated,
BA3011 & BA3021 combination w/ PD-1 (n=60); ROR2 positive dosing 1H 2022 ROR2 TmPS* 1; Platinum failure patients 10 # Note: STS = Soft Tissue Sarcoma; *TmPS= Tumor membrane Percent Score- Scores range from 0 to 100
Significant opportunity to fill treatment void in sarcomas Mecbo
- BA3011 SARCOMA Unmet Need for Sarcomas Large and Under-Appreciated No targeted therapies available for most soft tissue Commercial Opportunity sarcoma Bone sarcomas have no approved therapies after failure of frontline
regimens Low 5-year survival rates (~16.4% for late-stage ~17,000 diagnosed unresectable / metastatic cases in 2021 metastatic soft tissue sarcoma) Before withdrawal from market for failing Phase 3, Lilly's olaratumab
had sales of $562 million with a 50% CAGR, in less than 2 years Lower Regulatory Hurdles for Sarcoma Treatments 100% Approved therapies show improved 75% 1 ORRs of less than 15% 50% 25% 15% * * * * * * * ORR 0% * Approved Source: DRG. Soft
tissue sarcoma. Epi dashboard. 2020 1 Note: Objective response rates (ORR) is defined as the proportion of patients with tumor 5 size reduction of a predefined amount and for a minimum time period and is comprised of Median progression-free survival
(PFS) for approved therapies ranges from 2 - 7 months 2 complete responses and partial responses; Pembrolizumab ORR data from 2015-2016 11 3 4 Pembrolizumab ORR data from 2017 ORR for Gemcitabine treatment in combination with 5 Docetaxel CA
CANCER J CLIN 2020;70:200-229
Encouraging Phase I results with Mecbotamab Vedotin in refractory
sarcoma Mecbo - BA3011 PHASE 1 - SARCOMA Confirmed TmPS* 70; 1.8mg/kg Q3W or 2Q3W Evaluable Patients in Phase 1 at All Doses High TmPS 70 AXL+ 100 Low TmPS 70 or Not Evaluable $ TmPS=90 1.8mg/kg 80 Confirmed Partial
Response (PR) d1,8 60 AXL+ TmPS=100 40 1.8mg/kg AXL+ AXL+ AXL+ AXL+ AXL+ d1,8 TmPS=100 TmPS=90 TmPS=95 TmPS=70 TmPS=100 20 1.8mg/kg 1.8mg/kg 1.8mg/kg 1.8mg/kg 1.8mg/kg d1,8 d1,8 d1,8 0 2 Leiomyosarcoma Synovial Uterine (LMS) Sarcoma -20 LMS -40 LMS
* -60 1 (NED ) UPS * -80 UPS * Ewing -100 * Notes: All patients: Multiple cycles of antineoplastic agents received prior to starting treatment with BA3011 $ *AXL Tumor membrane Percent Score or TmPS = % Score 1+; Tissue biopsy from resection,
over 1 year old prior to trial entry 1 2 NED = No evidence of disease; Synovial sarcoma patient delayed treatment due to unrelated SAE led to progression 12 Maximum % Change from Baseline in Sum of Target Lesions
Predefined Interim Analysis: Decision Tree Mecbo - BA3011 PHASE 2
- SARCOMA ~10 patients w TmPS>=70 LMS Syn ~10 patients w TmPS>=70 STS Lipo For each Subgroup ~10 patients w TmPS>=70 up to 10 patients Others Monotherapy ~10 patients w TmPS>=70 No Go if 0 CR/PR and PFR12 week < 40% Osteo ~10 patients
w TmPS>=70 Go if 1 CR/PR or Bone Ewing ~10 patients w TmPS>=70 PFR12 week 40% ~10 patients w TmPS>=70 Others ~10 patients w CD20 pos Combo with PD-1 ~10 patients w CD20 neg 13
Preliminary observations from Phase 2 sarcoma study with Mecbotamab
Vedotin Mecbo - BA3011 PHASE 2 - SARCOMA Study enrolling as per plan with initial interim cohort of ~70 pts enrolled at EOY Reported good clinical activity in advanced refractory sarcoma population to date Several
cohorts already qualified to move into part 2 of the P2 study Safety profile continues to be well-differentiated st Full interim P2 study data cut made on March 31 w/ a targeted two scans per patient th Clinical data analysis
underway - topline interim update scheduled for May 4 earnings call Patient enrollment expected to continue through upcoming P2 interim stage FDA discussions 14
Complete response in 1/1 ROR2+ patient in stage IV multi-refractory
melanoma and partial response in 1/1 ROR2+ patient in head and neck squamous cell cancer (HNC) Ozurif - BA3021 Phase 1 - MELANOMA Two evaluable metastatic melanoma patients enrolled in Phase 1 trial 100 0.6 mg/kg (d1) 80 3.0 mg/kg (d1) 60 40
ROR2 - 20 0 -20 -40 -60 ROR2 + -80 -100 120 140 0 10 20 30 40 Time (weeks) Details: ROR+ Patient Prior treatment failure: nivolumab followed by nivolumab + ipilimumab combination achieved Melanoma confirmed by biopsy immediately
prior to BA3021 trial entry Complete Clearance of pulmonary metastases followed by normalization of adenopathy Response Continued CR Off treatment for approximately one year Phase 1 - HEAD and NECK SQUAMOUS CELL CANCER (HNC):
Additionally, Partial Response (-54%) observed in 1 / 1 ROR2 + (TmPS = 16%) HNC patient (refractory to four prior lines of therapy including cetuximab and pembrolizumab) 15 Change in target lesion from baseline (%)
Encouraging Phase I results in NSCLC refractory patients Phase 1 -
NSCLC Mecbo - BA3011 Ozurif - BA3021 Response at Variable Dosing Response at Variable Dosing 30% ROR2 + ROR2 - ROR2 + Not ROR2 + ROR2 + (**TmPS=100) (**TmPS=0) (**TmPS=45) Evaluable (**TmPS=95) (**TmPS=70) 1.2mg/kg d1,8 3mg/kg d1
3.3mg/kg d1 1.5mg/kg d1,8 3.3mg/kg d1 3mg/kg d1 20% 10% AXL - AXL - Not AXL + TmPS=0 TmPS=0 Evaluable TmPS=80 0% 1.5mg/kg d1,8 1.2mg/kg d1,8 1.2mg/kg d1 1.8mg/kg d1,8 PR -10% Suboptimal dose (1.2mg/kg 2Q3W) -20% Patient
experienced tumor shrinkage prior to -30% progression of metastatic * bone lesions Confirmed PR -40% Stage IV NSCLC squamous tumor: adenocarcinoma 10mm to 0mm on first scan -50% (multiple chemo PKIs and * pembrolizumab failure) -60% Note:
Not Evaluable (Strong, extensive fibroblastic stromal positivity reported) 16 Maximum Change from Baseline (%) Maximum % Change from Baseline in Sum of Target Lesions
Promising safety and tolerability profile emerging PHASE 1 AEs for all
doses CAB AXL-ADC Mecbo - BA3011 (all patients n=64) Overview Grade 1-2 (26%) AEs consistent with MMAE-based toxicity, including: Constipation o Reversible myelosuppression Grade 3 (3%) o Transient liver enzyme elevation Peripheral
Neuropathy o Metabolic disturbances All Grade 1-2 (28%) Few related SAEs Grade 1-2 (19%) Few related AEs leading to treatment discontinuation Diarrhea Grade 3-4 (3%) Constipation is believed to be an on-target mediated effect PHASE 1
& 2 AEs at P2-relevant doses No clinically meaningful on-target toxicity observed over background CAB AXL-ADC Mecbo - BA3011 Dosing 1.8mg/kg Q3W, Q2W, or 2Q3W (d1,8) Differentiated profile due to advantageous
pharmacokinetic (safety population Phase 1 & 2) characteristics of CAB ADCs BA3011 Characteristic (N=38) Any Adverse Events (AEs) 38 ( 100%) 1 2 15 ( 39%) Related AEs with CTCAE Grade 3 or 4 2 Any related serious AEs 4 ( 11%) Ozurif -
BA3021 2 0 Related AEs leading to death Related AEs leading to treatment Similar safety profile observed 2 (5%) 2 discontinuation 17 1 Note: CTCAE: Common Terminology Criteria for Adverse Events. The NCI Common Terminology Criteria
for Adverse Events is a descriptive terminology which is utilized for Adverse Event (AE) reporting. A 2 grading (severity) scale is provided for each AE term. As assessed by the investigator. Missing responses are counted as related. Grade 2
fatigue and peripheral neuropathy at 1.8mg/kg 2Q3W