Sun Pharma Advanced Research Company Limited has informed the Exchange about Investor Presentation
SPARC/Sec/SE/2022-23/060
October 13, 2022
National Stock Exchange of India Ltd., Exchange Plaza, 5th Floor, Plot No. C/1, G Block, Bandra Kurla Complex, Bandra (East), Mumbai – 400 051.
BSE Limited, Market Operations Dept. P. J. Towers, Dalal Street, Mumbai - 400 001.
Ref: Scrip Code: NSE: SPARC; BSE: 532872
Dear Sir/Madam,
Sub: Investor Presentation: Update on Clinical Programs and R&D Pipeline
to Regulation 30 of
Pursuant the SEBI (Listing Obligations and Disclosure Requirements) Regulations, 2015 and further to our letter dated September 29, 2022 bearing reference no. SPARC/Sec/SE/2022-23/056, we enclose herewith a copy of the Investor Presentation on the above mentioned subject, which is self-explanatory.
This is for your information and dissemination.
Yours faithfully,
For Sun Pharma Advanced Research Company Ltd.
Dinesh Lahoti Company Secretary and Compliance Officer ICSI Membership No. A22471
Encl: As above
Update on Clinical Programs and R&D Pipeline
13th October 2022
BSE:532872 NSE: SPARC BLOOMBERG: SPADV@IN REUTERS: SPRC.BO CIN:L73100GJ2006PLC047837
Disclaimer
This presentation and its contents should not be distributed, published or reproduced, in whole or part, or disclosed by recipients directly or indirectly to any other person. Any failure to comply with these restrictions may constitute a violation of applicable laws. Accordingly, any persons in possession of this presentation should inform themselves about and observe any such restrictions. This presentation may include statements which may constitute forward-looking statements. All statements that address expectations or projections about the future, including, but not limited to, statements about the strategy for growth, business development, market position, expenditures, and financial results, are forward looking statements. Peak sales forecast/potential in the presentation represent potential sales of the product/s for the commercialization partner. Forward looking statements are based on certain assumptions and expectations of future events. This presentation should not be relied upon as a recommendation or forecast by Sun Pharma Advanced Research Company Limited (“Company”). Please note that the past performance of the Company is not, and should not be considered as, indicative of future results. The Company cannot guarantee that these assumptions and expectations are accurate or will be realized. The actual results, performance or achievements, could thus differ materially from those projected in any such forward-looking statements. The Company does not undertake to revise any forward-looking statement that may be made from time to time by or on behalf of the Company. Given these risks, uncertainties and other factors, viewers of this presentation are cautioned not to place undue reliance on these forward looking statements.
The information contained in these materials has not been independently verified. None of the Company, its Directors, Promoters or affiliates, nor any of its or their respective employees, advisers or representatives or any other person accepts any responsibility or liability whatsoever, whether arising in tort, contract or otherwise, for any errors, omissions or inaccuracies in such information or opinions or for any loss, cost or damage suffered or incurred howsoever arising, directly or indirectly, from any use of this document or its contents or otherwise in connection with this document, and makes no representation or warranty, express or implied, for the contents of this document including its accuracy, fairness, completeness or verification or for any other statement made or purported to be made by any of them, or on behalf of them, and nothing in this presentation shall be relied upon as a promise or representation in this respect, whether as to the past or the future. The information and opinions contained in this presentation are current, and if not stated otherwise, as of the date of this presentation. The Company undertakes no obligation to update or revise any information or the opinions expressed in this presentation as a result of new information, future events or otherwise. Any opinions or information expressed in this presentation are subject to change without notice. This presentation does not constitute or form part of any offer or invitation or inducement to sell or issue, or any solicitation of any offer to purchase or subscribe for, any securities of the Company, nor shall it or any part of it or the fact of its distribution form the basis of, or be relied on in connection with, any contract or commitment therefor. No person is authorized to give any information or to make any representation not contained in or inconsistent with this presentation and if given or made, such information or representation must not be relied upon as having been authorized by any person. By participating in this presentation or by accepting any copy of the slides presented, you agree to be bound by the foregoing limitations. All brand names and trademarks are the property of respective owners.
2
SPARC © 2022Agenda
01
02
Overview Anil Raghavan
03
Biologics Nitin Damle
04
05
Financial Update Chetan Rajpara
Clinical Programs Siu-Long Yao
Preclinical NCE Program Vikram Ramanathan
3
SPARC © 2022Built a robust R&D organization
Innovating from India for the world, SPARC offers operating model validation
Successful track record of development and commercialization
Clinical pipeline targeting high-value opportunities
Through an innovation-focused R&D platform
2
3
10+
USFDA approved drugs (XelprosTM, ElepsiaTM)
NCEs targeting 6 clinical indications in development
Preclinical programs in R&D pipeline covering 3 therapy areas
2
NDAs submitted to USFDA in FY23
1
NDA targeted for submission in H2 FY23
USD 20Bn+
Combined peak sales potential for NCEs currently under clinical development
2
IND filings targeted by FY24
11
Partnerships with academic centers and commercial entities1
4
1. Partners include JHU, UCSF, Wash U at St Louis, University of Michigan, Scripps Research, Bioprojet, CMS, Sun Pharma, Tripoint Therapeutics, Biomodifying, and Visiox | USFDA = US Food & Drug Administration | NDA = New Drug Application | NCE = New Chemical Entity | IND = Investigational New Drug
SPARC © 2022Attractive portfolio built using a cost-efficient structure
Over 50% funded through non-dilutive revenue generated
2012
2016
2017
2021
Promoters’ share
Others
26%
25%
7%
46%
74%
75%
93%
54%
Rights issue 1 INR 198 cr / USD 41 mn
Rights issue 2 INR 250 cr / USD 38 mn
Preferential issue of convertible warrants 1 INR 500 cr / USD 75 mn
Preferential issue of convertible warrants 2 INR 1112 cr / USD 148 mn
USD 523 mn
USD 277 mn
Total investment till FY22
Revenues re-invested till FY22
5
SPARC © 2022Our strategy to address unmet clinical need has transformed
With a focus on novel biology as opposed to fast follower approach
Asset Distribution by Class
Asset Distribution by type
57%
14%
7%
43%
79%
FIC
BIC
NCE
Biologic
Complex Modalities
FIC – First in Class | BIC – Best in Class
Increasing proportion of
programs focusing on novel biology (potential first-in- class)
Investments in new modalities/complex platforms is now translating to tangible programs
Continued development of best-in-class assets for validated targets
Collaboration with external innovators as a key tenet of strategy to access early science
6
SPARC © 2022First-in-class innovation in three therapy areas
With 70% of the preclinical pipeline targeting novel hypotheses
Areas of interest
Lead FIC Program
Neurology
Oncology
Immunology
Restoring cellular function in the CNS to modify disease- course by: • Modulating oxidative stress
response Improving autophagic flux
• • Preventing misfolded protein aggregation
Modality-agnostic, tumor-targeted strategies to address indications that have limited treatment options
Pursuing novel
targets in immune cells and inflamed tissues to modulate inflammatory conditions
SCC-138
SBO-154
SCD-153
Internally developed NCE - vodobatinib
Selective c-ABL
inhibitor with good brain penetration and superior safety for Parkinson’s Disease (PD)
Currently in a Phase 2
clinical study
In-licensed anti-
MUC-1 antibodies from Biomodifying LLC
Developed antibody- drug conjugate asset for solid tumors
Currently in IND-
enabling preclinical development
Collaboration with
Johns Hopkins University
NCE targeting a novel pathway to address alopecia areata
Currently in IND-
enabling preclinical development
7
CNS = Central Nervous System | NCE = New Chemical Entity | IND = Investigational New Drug
SPARC © 2022 Expected cash inflow from warrants conversion
Cash runway till FY24, with potential extension from milestones and royalties
H2 FY23
H1 FY24
H2 FY24
Cash inflow from warrants conversion by Dec’22
USD 93 mn
Expected cash burn
USD 30 mn
USD 30 mn
USD 30 mn
Cash runway excluding milestones and royalties
8
SPARC © 2022Sezaby*: benzyl alcohol-free phenobarbital injection for neonatal seizures
Currently marketed formulations
Sezaby
Classified under DESI products by USFDA; approved only for safety between 1938 and 1962
Contain benzyl alcohol as a preservative which has been associated with “Gasping Syndrome” in neonates and low-birth weight infants
Granted Orphan Drug Designation for treatment of neonatal seizures Upon approval will be eligible of Orphan Drug Exclusivity NDA submitted in 2022 USFDA granted priority review of NDA PDUFA goal date of Nov’22 SPARC under advance discussion with potential partners for licensing commercialization rights of Sezaby
Sezaby as a trade name is conditionally accepted by the USFDA
9
DESI = Drug Efficacy Study Implementation | USFDA = US Food & Drug Administration | NDA = New Drug Application | PDUFA = Prescription Drug User Fee Act
SPARC © 2022Several high-yield assets graduating to next set of data events in the short term
Sharp execution focus to deliver key updates in the next 18-24 months
Licensing and commercialization of near-term assets
Continued progress of clinical NCEs
Early PoC for new platforms
Driving uptake of
and
Collaborate with Visiox Pharma for commercialization of PDP- 716 and SDN-037
Licensing of Sezaby to potential partner
Vodobatinib CML read out in FY24
IND filing for SCD-153 in FY23 and for SBO-154 in FY24
Vodobatinib PD PROSEEK Phase 2 readout in FY24
SCO-120 clinical PoC in FY24
In-licensing of preclinical assets
NCE = New Chemical Entity | PoC = Proof-of-Concept | CML = Chronic Myeloid Leukemia | IND = Investigational New Drug
10
SPARC © 2022Pipeline overview & key upcoming milestones
Asset / Program
MoA
Indication
Discovery Preclinical
Phase 1
Phase 2
Phase 3/ Registration Study
Upcoming Catalyst
Partner
Vodobatinib (SCC-138)
c-ABL Inhibitor
Vodobatinib (SCO-088)
BCR-ABL Inhibitor
Parkinson’s Disease
Lewy Body Dementia1
Alzheimer’s Disease
Refractory CML
SC0-120
SB0-154
Selective ERα Receptor Degrader
Metastatic Breast Cancer
Anti-MUC-1 ADC
Multiple Tumors
Vibozilimod (SCD-044)
Selective S1PR1 agonist
SCD-153
Undisclosed
Psoriasis
Atopic Dermatitis
Alopecia Areata
PoC data from PROSEEK study in FY24
PoC data in FY24
Pivotal data in FY24
Phase 1 data in FY24
IND filing targeted in FY24
IND filing targeted in FY23
Preclinical Assets
10+ preclinical assets under development to ensure a robust pipeline for future growth
Neurology
Oncology
Immunology
1. Investigator Initiated Study | MoA = Mechanism of Action | ADC - Antibody-Drug Conjugate PoC = Proof of Concept | CML = Chronic Myeloid Leukemia | S1PR1 = Sphingosine-1- Phosphate Receptor 1 | ERα = estrogen receptor α | IND = Investigational New Drug
11
SPARC © 2022Clinical Programs
Siu-Long Yao
Vodobatinib in CML (SCO-088)
A safer, last-line option for heavily pre-treated patients
Vodobatinib for CML (SCO-088)
Potent and selective inhibitor of BCR-ABL1
Healthy volunteer study
Patient studies
Clinical study design
Single Ascending Dose (SAD) and Food Effect studies in healthy volunteers (N = 40)
Multiple Ascending Dose (MAD) study in patients (N = 53)
Enrollment ongoing
Pivotal efficacy study in refractory patients
CP-CML N = 59
BP-CML N = 43
AP-CML N = 43
Single arm study, Ph+ CML patients
refractory and/or intolerant to ≥3 TKIs including ponatinib
Participating countries: USA, Belgium, France, Italy, Spain, Romania, Hungary, Singapore, UK, Korea
14
CP = chronic phase | AP = accelerated phase | BP = blast phase | Ph = Philadelphia chromosome | TKI = Tyrosine Kinase Inhibitor | CML = Chronic Myeloid Leukemia NCT02629692
SPARC © 2022Vodobatinib (SCO-088) MAD study outcome
Major Cytogenetic Response (MCyR) rate more than doubles in CP-CML patients treated with vodobatinib
Cytogenetic Response
N=42
MCyR (29%)
Baseline
71
12
17
MCyR (67%)
Best Response
33
10
57
0
20
40
60
80
100
% patients
CyR = Cytogenetic response | MCyR = Major cytogenetic response | MCyR = PCyR + CCyR | Data presented at 2021 ASH Annual Meeting | Numbers rounded-off to nearest integer | CP-CML = Chronic Phase Chronic Myeloid Leukemia
No response
Partial CyR
Complete CyR
15
SPARC © 2022Vodobatinib (SCO-088) MAD study outcome
Twenty-fold improvement in Major Molecular Response (MMR) rate in CP-CML patients treated with vodobatinib
Molecular Response
N=42
MMR (2.8%)
Baseline
98
0.00
2
MMR (43%)
Best Response
57
2
41
0
20
40
60
80
100
% patients
Major Molecular Response | Data presented at 2021 ASH Annual Meeting | Numbers rounded-off to nearest integer | CP-CML = Chronic Phase Chronic Myeloid Leukemia
No response
MMR maintained
MMR achieved
16
SPARC © 2022Vodobatinib (SCO-088) MAD study outcome
Excellent efficacy and safety
Patients on study after:
1 year: 71.7% 2 years: 52.8% 3 years: 37.7%
Median duration on study = 23.9 months (range: 0.1 - 65.17 months)
Discontinued study drug
On treatment
0
10
20
30
40
50
60
70
Duration in months
17
Data cutoff: 1st September 2022
SPARC © 2022 Next steps
Additional data to be presented at upcoming clinical conferences: the 2022 ESH John Goldman Conference and the 2022 ASH Annual Meeting
Pivotal study readout in FY24
18
SPARC © 2022Vodobatinib for Neurodegenerative diseases (SCC-138)
A potential first- in-class disease modifying therapy targeting c-Abl
c-Abl: a critical component of neurodegeneration
Substantiated by multiple research groups
Ubiquitous expression in nucleated cells
• Expressed in all parts of the CNS (brain and spinal column, and peripheral neuronal tissue)
Pivotal role in promoting
neurodegeneration
• Under oxidative stress, c-Abl is activated and phosphorylates a number of key substrates that bring about programmed death of oxidatively-stressed neurons
CNS = Central Nervous System
20
SPARC © 2022 Vodobatinib improved motor and cognitive function in the PFF-induced mouse model1
Vodobatinib at 45 mg/ kg improves PFF-induced movement disorder- related deficits in Turning Time and Descending Time in the Pole test
) c e S (
e m
i t g n n r u T
i
Vodobatinib treatment improves PFF-induced deficits in Grip Strength
)
m g (
e c r o f
s b m
i l
e r o F
Turning Time in Pole Test
Descending Time in Pole Test
.
3 4 0 0 0 > = p
p=>0.9999
.
9 9 9 9 0 > = p
1 1 1 0 0 = p
.
PBS+ Placebo
PBS+ Vodobatinib 45mg/kg
PFF+ Placebo
PFF+ Vodobatinib 15mg/kg
PFF+ Vodobatinib 45mg/kg
Grip Strength: Fore Limbs
8 4 5 3 0 = p
.
8 2 0 0 0 = p
.
3 0 7 5 0 = p
.
4 8 1 0 0 = p
.
20
15
10
5
0
250
200
150
100
50
0
p=>0.0001
p=>0.9999
5 0 2 0 0 = p
.
-
3 0 0 0 0 = p
.
PBS+ Placebo
PBS+ Vodobatinib 45mg/kg
PFF+ Placebo
PFF+ Vodobatinib 15mg/kg
PFF+ Vodobatinib 45mg/kg
Grip Strength: All Limbs
.
9 9 9 9 0 > = p
5 5 2 0 0 = p
.
3 8 3 1 0 = p
.
2 2 0 0 0 = p
.
) c e S (
e m
i
i t g n d n e c s e D
)
m g (
e c r o f
s b m
i l
l l
A
20
15
10
5
0
500
400
300
200
100
0
PBS+ Placebo
PBS+ Vodobatinib 45mg/kg
PFF+ Placebo
PFF+ Vodobatinib 15mg/kg
PFF+ Vodobatinib 45mg/kg
PBS+ Placebo
PBS+ Vodobatinib 45mg/kg
PFF+ Placebo
PFF+ Vodobatinib 15mg/kg
PFF+ Vodobatinib 45mg/kg
21
1. Study conducted at the Ted Dawson Lab, Johns Hopkins University | PBS = Phosphate-buffered saline | PFF = Preformed fibril
SPARC © 2022 Vodobatinib protects dopaminergic neurons in the AAV mutant α-synuclein (hA53T) rat model – dopamine transporter expression
1 2 1 - I T R I 5 2 1
l
a t a i r t S
c i f i c e p S
e u s s i t
m a r g / i C n g n d n B
i
i
1.0
NS
**
**
*
NS
0.8
0.6
0.4
0.2
0
Vodobatinib treatment protects
against dopaminergic neuronal loss measured by radiolabeled 125I labeled RTI-121 binding in the striatum
• Comparison of un-operated left
hemisphere (L) and operated right hemisphere (R, injected with & expressing the AAV) shows that 45 mg/kg dose provides protection of dopaminergic neurons
L
R
AAV EV
L
R
L
R
L
R
L
R
AAV hA53T α-synuclein
Vehicle
Vehicle
Vodobatinib 15mg/kg
Vodobatinib 30mg/kg
Vodobatinib 45mg/kg
AAV = Adeno Associated Virus | EV = Empty Vector
22
SPARC © 2022 Vodobatinib for PD (SCC-138)
Recruitment on track to achieve enrollment target in PROSEEK
Screening
Randomization
Placebo (N=168)
Vodobatinib 384mg (N=168)
Vodobatinib 192mg (N=168)
PART 1 Weeks 0 to 40
PART 2 Weeks 41 to 76
Vodobatinib 384mg
Vodobatinib 192mg
Patient continues into extension part of protocol
PROSEEK
77 sites across US, Europe and India functional; recruitment ongoing to complete enrollment in FY23
Over 70% patients randomized
(N=349)*
Extension study
Patients enrolled to establish long-
term safety and tolerability
*As of 14th Sept 2022 | PROSEEK = A Phase 2 Study In Early Parkinson’s Disease Patients Evaluating The Safety And Efficacy Of Abl Tyrosine Kinase Inhibition Using K0706 | K0706 = Vodobatinib PD (SCC-138) | NCT03655236
23
SPARC © 2022Opportunities beyond PD: Lewy Body Dementia
Recruitment ongoing in an investigator-initiated clinical trial at Georgetown University
RANDOMIZATION
PLACEBO
(N=15)
VODOBATINIB
96mg (N=15)
VODOBATINIB
192mg (N=15)
Recruitment ongoing in a 12-week Phase 2 study
Safety and tolerability being evaluated as a
in collaboration with Georgetown University
primary outcome
50% patients randomized
Concentration of LBD-related plasma and CSF biomarkers form the set of secondary outcome measures
24
SPARC © 2022Next steps
Parkinson’s Disease
Lewy-Body Dementia
Complete recruitment in PROSEEK
PROSEEK study readout in FY24
Complete recruitment by FY24 in the Georgetown University study
Study readout in FY24
25
SPARC © 2022Vibozilimod (SCD-044) – A selective S1PR1 agonist
A safer alternative to JAK inhibitors
Vibozilimod (SCD-044) for Psoriasis and Atopic Dermatitis
An opportunity to improve oral standard-of-care in dermatology
Vibozilimod is a Best-in-Class S1PR1 modulator with excellent safety
S1PR1 Modulator Landscape
Vibozilimod (SCD-044)
Fingolimod is the first-in-class S1PR agonist
approved, but not suitable for some indications because of safety concerns
Developed in collaboration with a French
biotech company, Bioprojet. SPARC in-licensed Bioprojet’s share of IP in 2019
Multiple S1PR1 modulators are approved
Highly-selective for S1PR1 over S1PR2 and
(siponimod and ozanimod) for non-dermatology indications; vibozilimod has opportunity to lead the field in dermatology
Recent safety concerns related to JAK inhibitors
increase the significance of S1PR1 agonists as a ‘class alternative’ in several autoimmune disorders, particularly in dermatology
S1PR3, which can be associated with serious side effects
Established preclinical and early clinical validation
Currently targeting atopic dermatitis, psoriasis
and other autoimmune disorders
Potential synergy with other mechanisms in IBD
– like IL-23 blockade
S1PR1 = Sphingosine-1-Phosphate Receptor-1 | JAK = Janus Kinase | IP = Intellecual Property | IL-23 = Interleukin-23 | IBD = Inflammatory Bowel Disease
27
SPARC © 2022Vibozilimod (SCD-044) for Psoriasis
Phase 2 study design
Screening 4 Weeks
Part I:16 Weeks
Part II:16-28 Weeks
Part III:28-52 Weeks
Follow-up Week 56
Placebo
Vibozilimod Intermediate Dose
s t n e m
s s e s s A g n n e e r c S
i
Vibozilimod Low Dose
Vibozilimod Intermediate Dose
Vibozilimod High Dose
PASI50 response Continue to Vibozilimod Low Dose
<PASI50 response Switch to Vibozilimod High Dose
Vibozilimod High Dose
Continue the assigned treatment
< PASI75 response at week 28
Discontinue
PASI75 response at week 28
Continue on existing regimen
Primary endpoint – Proportion of patients with PASI75 response at week 16
240 patients across
three dose levels and placebo. Currently in early stage ramp-up
Study now open in the US. Expected to expand to Latin America and Europe to accelerate in the coming months
p u - w o
l l
o F
e e r f
t n e m t a e r T
PASI = Psoriasis Area and Severity Index | NCT04566666 | (SCD-044-19-14, Version 1, September 23, 2020)
28
SPARC © 2022 Vibozilimod (SCD-044) for Atopic Dermatitis
Phase 2 study design
Screening 3 Weeks
Part I:16 Weeks
Part II:16-32 Weeks
Follow-up 4 Weeks
Placebo
Vibozilimod Intermediate Dose
Vibozilimod High Dose
Vibozilimod Low Dose
Vibozilimod Intermediate Dose
Vibozilimod High Dose
s t n e m
s s e s s A g n n e e r c S
i
p u - w o
l l
o F
e e r f
t n e m t a e r T
Primary endpoint – Proportion of patients with EASI-75 response at week 16
240 Patients across three dose levels and placebo. Currently in early stage ramp-up
Study now open in the US. Expected to expand to Latin America and Europe to accelerate in the coming months
EASI = Eczema Area and Severity Index | NCT04684485 | (SCD-044-19-14, Version 1, November 9, 2020)
29
SPARC © 2022 SCO-120 for HR+/ HER2- MBC
An oral SERD with brain penetration
Current treatment paradigm
Dominated by endocrine therapy except in patients with visceral disease
Early breast cancer
1st line
2nd line
Endocrine backbone
AI / Tamoxifen
AI
Fulvestrant / Exemestane
Combination partner
CDK 4/6i
CDK 4/6i or mTORi or PI3Ki
Fulvestrant is currently the only SERD available for patients failing 1L setting
It is limited by intramuscular (IM) administration and its inability to address mutations
Elacestrant phase 3 study met its co-primary endpoints of improved PFS in patients with wild type and mutant disease in 2nd line patients.
CDK4/6i has emerged as the gold standard in 1L but requires an endocrine backbone
SERDs in development have the potential to become that backbone
SERD – Selective Estrogen Receptor Degrader | AI – Aromatase Inhibitor | ESR1 – Estrogen Receptor 1 CDK – Cyclin-Dependent Kinase | PI3K – Phosphoinositide-3-Kinase | PFS – Progression Free Survival | mTORi - Mammalian Target of Rapamycin inhibitor
31
SPARC © 2022 SCO-120: Oral SERD for HR+/HER2- MBC
Clinical study design
Single Ascending Dose (Part A)
Food Effect (Part B)
Multiple Ascending Dose (Part C)
Phase 1 Healthy Volunteer Study Design
Double blind, placebo controlled, single oral dose
Open label, two period, cross over, single dose, fast/fed study
Double blind, placebo controlled, once daily, 14 day repeat dose
Multiple Ascending Dose study
Phase 1 Patient study
HR+/HER2- metastatic breast cancer patients that have failed at least 1 prior endocrine therapy and no more than 3 prior chemotherapy treatments
Dose escalation (MTD/RP2D, safety) (N~44)
MTD/RP2D reached
Dose expansion
(Safety & Preliminary efficacy) (N~105)
Part a: ESR1 mutations
Part b: Resistant to AI ± CDK4/6i
Part c: Resistant to AI & Ful+ CDK4/6i
Part d: Secondary brain metastases to breast
cancer
MBC = Metastatic Breast Cancer | MTD = Maximum Tolerated Dose | RP2D = Recommended Phase 2 Dose | ESR1 = Estrogen Receptor 1 | AI = Aromatase Inhibitor | CDK = Cyclin Dependent Kinase | Ful = Fulvestrant
32
SPARC © 2022Next steps
MAD in patients study completion and read out in FY24
Phase 2 initiation in FY24
Target NDA submission in FY27
33
SPARC © 2022Biologics
Nitin Damle
SBO-154 (Anti-MUC-1 ADC)
Targeting an antigen expressed in a wide spectrum of tumors
SBO-154: Anti-MUC-1 ADC
Novel approach to target α/β complex, with an opportunity to target multiple tumor types
Tumor agnostic opportunity in-licensed from
Biomodifying LLC*
MUC-1 expressed extensively in majority of
tumors
Preclinical PoC of anti-tumour efficacy of
anti-MUC-1 targeted ADC established
Most anti-MUC-1 mAbs under development
target VNTR in the MUC-1α
Circulating MUC-1α in plasma and in peritumoral space block meaningful tumor targeting by MUC1α-targeted therapies
Primary reason for the lack of efficacy
No directly competing agents targeting
α /β junction
Potential to be an anchor for other
constructs like bi-specific/multi-specific antibodies, naked mAb, etc.
α Subunit
β Subunit
C
N
R T N V
AR20.5 C242 PAM4 DS6 KL6 5E5 2D9 PankoMab TAB004
*Anti-MUC-1 antibodies licensed from Biomodifying LLC | MUC-1 - Mucin-1 | ADC - Antibody Drug Conjugate | PoC – Proof-of-concept
36
SPARC © 2022 Anti-MUC-1 mAbs* internalize in pancreatic carcinoma cells
Alexa 647 labelled 1° Ab
Alexa 488 labelled 2° Ab
Hoechst
Merged
BF
1 - C U M
- i t n A
b a m i x u t i R
Red fluorescence is associated with anti-MUC-1 antibody, green fluorescence is associated with anti-human Fc-γ antibody & Hoechst dye stains nucleus and is blue in colour
*Anti-MUC-1 antibodies licensed from Biomodifying LLC
37
SPARC © 2022SBO-154 strongly inhibits growth of MUC-1 expressing tumors
Established in subcutaneous pancreatic carcinoma xenografts
) 3
m m
(
l
e m u o V r o m u T
3000
2500
2000
1500
1000
500
0
0
Regimen: Q7D x 3, i.p.
Free Payload
Vehicle, 10ml/kg
Rituximab-DC
SBO-154, low dose
Nab-PTX
SBO-154, medium dose
SBO-154, high dose
7
14
21
28
35
Days Post Treatment Initiation
Tumor staging
Tumor monitoring
Dose-dependent efficacy observed
with SBO-154, with sustained regression observed at high-dose
Rituximab-drug conjugate and
paclitaxel do not show similar activity
-33 to -63
0
7
14
Cell inoculation
Dosing
DC = Drug Conjugate | Nab-PTX = Paclitaxel
38
SPARC © 2022 SBO-154 causes regression of large tumor mass xenografts of a pancreatic carcinoma cell line
Tumor staging
Treatment
Tumor growth period (days)
) 3
m m
(
l
e m u o V r o m u T
DC = Drug Conjugate
Treatment: ip Q7Dx3
Vehicle
Rituximab-DC
SBO- 154
Large tumor study is used
to determine cytoreductive potential
SBO-154 but not isotype
matched control (rituximab- DC) causes significant regression of large established pancreatic tumor xenografts
39
SPARC © 2022 Next steps
IND enabling tox studies completion
Pre-IND meeting
IND filing in FY24
40
SPARC © 2022Preclinical NCE Program
Vikram Ramanathan
SCD-153 for Alopecia Areata
A potential first-in-class opportunity in an autoimmune disease with significant unmet need
Alopecia Areata – Autoimmune disease causing hair loss
Hair follicles lose immune privilege and they move into Telogen (resting) phase
Alopecia Areata is characterized by
Rapid progression of hair follicle from anagen (growing) phase to catagen (transition) phase to telogen (resting) phase
Collapse in immune privilege in hair
follicle bulb
CD4+ and CD8+ T cells infiltrate and
damage the hair bulb
NKG2D positive CD8+ T cells are the major
effectors of hair follicle damage
Alters normal hair growth cycle and causes
hair to fall out
However, the hair follicle structure and
stem cells are preserved, suggesting
potential for hair growth
Adapted from Nature Reviews. Disease Primers. 3:17011, 2017
43
SPARC © 2022 SCD-153 stimulates hair growth in animal models
C57BL/6 telogen - anagen alopecia model
Vehicle, QOD, 2 applications
SCD-153, QOD, 2 applications
Tofacitinib, QOD, 2 applications
Female mice, 8.5 weeks, Dorsal hair clipped. Treated on right side, left side is untreated. QOD: every other day
SCD-153 stimulates robust hair growth after 2 doses given on alternate days
Promotes re-entry into anagen possibly via activation of stem cells at the base of the hair follicle
44
SPARC © 2022SCD-153 stimulates hair growth in animal models
C3H/HeJ alopecia areata immune disease model
Before
After
Untreated
Treated
Red: Untreated
Green: Treated
Robust hair growth in a disease model Decrease in CD8+ immunostaining proximal to hair follicles. Reduction in “swarm of bees”
Decrease in gamma-interferon and CTL gene
signature
45
SPARC © 2022Next steps
IND enabling tox studies completion
IND filing in FY23
46
SPARC © 2022Financial Update
Chetan Rajpara
SPARC © 2022Financial summary
Year
USDINR
Total Income
Total Expenses
Exceptional Item
FY18
FY19
FY20
FY21
FY22
Q1FY23
64.46
69.95
70.91
74.23
74.49
77.16
83
329
49
196
342
-
87
399
-
258
410
-
144
347
0
Profit / (Loss) after Tax
(197)
(145)
(312)
(151)
(203)
Total Income
Total Expenses
Exceptional Item
12.9
51.1
7.6
28.1
48.9
-
12.2
56.3
-
34.8
55.2
-
19.3
46.6
-
INR Cr
29
111
0
(82)
USD Mn
3.7
14.4
-
Profit / (Loss) after Tax
(30.6)
(20.8)
(44.1)
(20.4)
(27.3)
(10.7)
48
SPARC © 2022Cash and liquidity
Issued convertible warrants for Rs. 1,112 Cr (~USD 148 Mn) in July 2021 by way of preferential issue
Received Rs. 409 Cr (~USD 55 Mn) being 25% payable on application & upon conversion of warrants
Balance Rs. 703 Cr (~USD 93 Mn) to be received by Dec 2022 upon conversion of warrants by investors
Line of credit from parent company Rs. 250 Cr (~USD 31 Mn) and bank facility for Rs. 245 Cr (~USD 31
Mn) in place, of which Rs. 183 Cr (~USD 23 Mn) is utilized as on Sept 30, 2022
Obtained shareholders’ fresh approval in Sep 2022 for raising additional sum up to Rs. 1,800 Cr (~USD 225
Mn) by way of issuance of fresh equity or debt
49
SPARC © 2022THANK YOU
The SPARC Logo is a trademarks of Sun Pharma Advanced Research Company Ltd . In addition to Company data, data from market research agencies, Stock Exchanges and industry publications has been used for this presentation. This material is for use during an oral presentation; it is not a complete record of the discussion. This work may not be used, sold, transferred, adapted, abridged, copied or reproduced in whole on or in part in any manner or form or in any media without the prior written consent. All product names and company names and logos mentioned herein are the trademarks or registered trademarks of respective owners
SPARC © 2022