SONNET Corporate Presentation Cowen 40th Annual Health Care Conference BioTherapeutics March 2020 This presentation contains forward looking statements that do not guarantee future performance
Forward Looking Statements This presentation contains forward-looking statements about Sonnet BioTherapeutics based on management’s current expectations which are subject to known and unknown uncertainties and risks. Words such as “anticipated,” “initiate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” “may,” and variations of these words or similar expressions are intended to identify forward-looking statements. Our actual results could differ materially from those discussed due to a number of factors, including, but not limited to, our ability to raise additional equity and debt financing on favorable terms, the success of our R&D programs, our ability to obtain regulatory approval of our clinical assets and other risk factors. We are providing this information as of the date of this presentation and do not undertake any obligation to update any forward-looking statements contained in this presentation as a result of new information, future events or otherwise. Unless the context requires otherwise, references to “Sonnet,” “Company,” “we,” “us” and “our” refer to Sonnet BioTherapeutics. 2
Powering a New Wave of Immune Therapeutics Leadership Highly experienced executive team with a deep knowledge of biopharmaceutical drug • discovery and development Platform Proprietary Fully Human Albumin Binding (F H AB) platform provides considerable payload • flexibility with asset generation capabilities across major biologic drug classes Technology Targeted delivery with increased in vivo efficacy ▪ Single or bispecific mechanism of action ▪ Extended pK ▪ Therapeutic Corporate strategy comprises an internal therapeutic pipeline of oncology candidates, • with external business development initiatives underway across oncology, autoimmune Focus and inflammatory diseases Recent acquisition of IL-6 therapeutic candidate (Phase 1 completed) • Clinical efficacy studies with recombinant formulation of low-dose IL-6 in ▪ Chemotherapy-Induced Peripheral Neuropathy (CIPN) to commence year-end 2020 Platform expansion capability into vaccines, antibody drug conjugation and CAR-T • technology 3
Pipeline Overview Program Indications Discovery Pre-Clinical Phase I Next Milestone: Chemotherapy Induced Pilot Efficacy SON-080 (low dose IL-6) Peripheral Neuropathy Study Initiation Phase 1b/2a Diabetic Peripheral Neuropathy SON-081 (low dose IL-6) Study Initiation Undisclosed Solid Tumor GLP Tox SON-1010 (IL12-F H AB) F H AB Platform Undisclosed Solid Tumor Non-GLP Tox SON-1210 (IL12-F H AB-IL15) Preclinical Early Stage Cancer SON-2014 (GMcSF-F H AB-IL18) Efficacy Preclinical SON-3015 (Anti-IL6-F H AB-Anti-TGF β ) Tumor and Bone Metastases Efficacy 4
Pipeline: Multiple Points of Intervention IL-18 Naïve Antigen T-cell Antigen Lymph Tumor Fragments Mature Dendritic Antigen Cell (antigen Effector cells: receptors presenting) 1. Activate other immune cells 2. Kill “target cells” Activated T-cell Memory cells: 1. Circulate months → years Immature 2. Ready to rapidly respond to Dendritic Cell same antigen again Replication of Antigen Activated T-cell T-cell antigen-specific T-cells become Recognition APC Interaction Activation T-cells specialized GM-CSF IL-12 IL-15 5
Sonnet’s Technology Advantage KEY FEATURES Sonnet’s Fully Human Albumin Binding Flexible Linkers (F H AB) technology utilizes a single chain Fully Human Construct antibody fragment (scFv) capable of Low/No immunogenicity • Therapeutic delivering one or two active drug Single- or Bi-specific design Payload B • compounds Targeted Delivery Therapeutic payloads attached via • High efficacy with low side effects • flexible linker peptides GP60- and SPARC-driven uptake • Therapeutic Payload A Following administration, Sonnet’s F H AB- Enhanced pK derived candidates bind to and “hitch - Extended dosing intervals • hike” on endogenous human serum FcRn binding • albumin (HSA) for transport to target Human Serum Small Size with Linear Flexibility tissues Albumin Optimized tumor penetration • F H AB has been designed to bind, • Mammalian Cell Production (CHO) unbind and rebind to albumin in an Glycosylated • on-and-off fashion through a physical Sonnet F H AB complex taken bonding mechanism, obviating the Modular up through GP60- and need for chemical conjugation Off-the-shelf system SPARC-mediated binding • Rapid asset development • 6
F H AB: Defining A Better Platform Technology F H AB PEGylation IgG/Fab Mechanism Single or Bispecific Single Single or Bispecific pK +++ ++ +++ Glycosylated Yes No Yes Tumor Targeting +++ - ++ ++++ +++ ++ Tumor Penetration 25-85 kD ~80 kD 100-300 kD 7
F H AB: Superior Uptake and Retention in Tumor Tissue An in vivo demonstration of SPARC-mediated binding with optimized retention using albumin Western blot analysis of Mouse 4T1 (TGF β - positive tumor @ ~150mm 3 ) extracts from mice terminated at 0.5, 4, 12 and 24-hours post IV injection with 100 µg/mouse of F H AB, anti-TGF β or anti-TGF β -F H AB. Results show superior accumulation and retention of F H AB in the tumor F H AB alone Anti-TGF β , no F H AB Anti-TGF β -F H AB • F H AB - Present at 0.5 hours, peaks at 4 hours and detectable through 24 50kD hours. • Anti-TGF β - Present at 0.5 hours then declines at 4 hours and undetectable 0.5 4 12 24 0.5 4 12 24 0.5 4 12 24 hours at 12 and 24 hours. • Anti-TGF β -F H AB – Present at 0.5 hours. and detectable through 24 hours. 25kD 8
F H AB: Enhanced Pharmacokinetics Comparing the pharmacokinetic (pK) behavior of naked IL-12 and IL-15 versus the same interleukins linked to Sonnet’s F H AB Method: 8 mice C57B/ TP, Age 9.5 weeks dose IV, sacrificed @ 5, 15, 30 mins, 1, 2, 4, 8, 24 & 48 hrs. Serum tested by ELISA IL12-F H AB IL12 WT IL15 WT IL15-F H AB IL15 WT IL15-A10M3 10,000,000.00000 10,000,000.00000 Protein Concentration ( pg/ml ) Protein Concentration ( pg/ml ) 1,000,000.00000 1,000,000.00000 Fusion to F H AB increased 100,000.00000 100,000.00000 t 1/2 β = 9.5 hrs the plasma half-life of IL-12 t 1/2 β ~ 7.0 hrs 10,000.00000 10,000.00000 > 4x and IL-15 >10X 1,000.00000 1,000.00000 t 1/2 β = 0.6 hrs IL-12 MW = 70kd vs IL-15 MW=13kd t 1/2 β = 2.5 hrs* 100.00000 100.00000 10.00000 10.00000 * IL12 pK in Mice ~ 3 hrs J. Immunol. 164, 839-847 * IL15 pK in Mice ~ 0.5 hrs 2012 PLoS ONE 7(2): * IL12 pK in Mice ~ 3 hrs J. Immunol. 164, 839 – 847 1.00000 1.00000 0 5 10 15 20 25 30 0 5 10 15 20 25 30 Time (Hours) Time (Hours) 9
SON-1010: Significantly Improved Tissue Distribution 1000 * Equal molar IL-12 concentration Single Dose Average Total Protein Concentration SON-1010 ELISA analysis of serum, spleen and tumor IL-12 shows high 100 levels in each for IL12- F H AB treated mice as (ng/ml) compared to naked IL-12 treatment. 10 Concentrations of IL-12 were increased in serum, tumor and spleen, 128- fold, 5.6-fold and 18-fold, respectively, over mice 1 dosed with naked IL-12. Serum Tumor Spleen IL-12 (20 µg) IL12-F H AB (30 µg) * 10
SON-1010: Extended IFN- γ Release With Reduced Tumor and Reciprocal Spleen Weight vs Naked IL-12 IFN- Tumor Weight Spleen Weight * ** 0.3 0.4 ANOVA: P=0.0081 ANOVA: P=0.0061 Placebo * 2500 IL12-FHAB 1µg 0.3 0.2 2000 IL12-FHAB 3µg Grams Grams 0.2 IL-12 1µg 1500 pg/ml 0.1 IL-12 3µg 0.1 1000 0.0 0.0 in AUC & Exposure 500 o o ) ) ) ) e) e) ) ) e Placebo IL12-FHAB IL12-FHAB IL-12 IL-12 e Placebo IL12-FHAB IL12-FHAB IL-12 IL-12 1µg 3µg 1µg 3µg 1µg 3µg 1µg 3µg 0 0 2 4 6 Day 5 Day 5 Days Summary: IL12-F H AB is more effective than naked IL-12 in reducing tumor weight, at equivalent doses • Reduction in tumor weight correlates with increase in spleen weight • IFN- γ levels are ~10x greater with longer pK • 11
SON-1010 vs naked IL-12: Dose Level Comparisons Tumor Volume Changes Between Groups on Day 10 Post Treatment 3000 Single Dose IL-12 vs IL12-F H AB Dose-dependent reduction in tumor 2500 G1: Vehicle volume with improved 2000 survival G2: IL-12 Final Tumor Volume (mm 3 ) * 3µg G3: IL12-F H AB 1500 Superior to naked IL-12 G4: IL-12 1000 10µg * G5: IL12-F H AB Favorable toxicity as 500 measured through body G6: IL-12 * 20µg weight analysis 0 G7: IL12-F H AB Markers of CRS showed * Equal molar IL-12 concentrations no increase at doses <20 µg Treatment Groups All asterisks are compared to Vehicle group with one-way ANOVA analysis * <0.05 ** <0.01 *** <0.001 12
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