Innovation-Focused ADC Company Corporate Overview September 2018 - - PowerPoint PPT Presentation

Corporate Overview

September 2018

Science-Based Innovation-Focused ADC Company

Forward-Looking Statements

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This presentation, in addition to historical information, contains certain forward- looking statements made pursuant to the Private Securities Litigation Reform Act of

• 1995. Such statements may involve significant risks and uncertainties, and actual

results could differ materially from those expressed or implied herein. Factors that could cause such differences include, but are not limited to, new product development (including clinical trials outcome and regulatory requirements/actions); competitive risks to marketed products; forecasts of future operating results; availability of required financing and other sources of funds on acceptable terms, if at all; as well as those discussed in the Company's filings with the Securities and Exchange Commission.

Our Company Vision for Value Creation

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Immunomedics is deeply committed to become the leading antibody-drug conjugate (ADC) company worldwide delivering breakthrough therapies to treat complex cancers and transform patient outcomes

First-in-class ADC Platform

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Linker for SN-38

SN-38 Payload

• 1. SN-38 more potent than

parent compound, irinotecan

• 2. In xenograft models, ADC

delivers up to 136-fold more SN-38 than irinotecan Linker for SN-38

• 1. Hydrolysable linker for payload

release

• 2. High drug-to-antibody ratio (7.5:1)

Suite of Humanized Antibodies for Creating ADCs

• 1. hRS7, used in sacituzumab govitecan, targets Trop-2 for solid cancers
• 2. Labetuzumab, used in IMMU-130, targets CEACAM5 for colorectal

cancer

• 3. IMMU-114, used in IMMU-140, targets HLA-DR for solid and liquid

cancers

Sacituzumab Govitecan, an Antibody-Drug Conjugate for Targeted Drug Delivery to Solid Cancers

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• Target: Trop-2

– Pan-epithelial cancer antigen with broad expression in many different cancers – ≥80% of patients have moderate to strong expression by immunohistochemistry – Internalizes upon antibody binding - ideal target for drug delivery with antibody-drug conjugates

• Antibody: Humanized RS7-3G11

– Binds human breast, lung, colon, renal, prostate, urothelial, and many other solid cancers

Trop-2 expression in TNBC liver tumor biopsy

Significant Progress with Sacituzumab Govitecan

• vs. Key Milestones

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• BLA submission for 3rd–line metastatic triple-negative breast cancer (mTNBC) accepted and granted

Priority Review by FDA

– PDUFA date set for January 18, 2019

• Enhanced supply chain by entering into a long-term manufacturing partnership agreement with Samsung

for commercial-scale production of hRS7

• Initiation of pivotal Phase 2 TROPHY U-01 study in metastatic urothelial cancer (mUC)
• Multiple clinical/preclinical collaborations to advance into earlier lines of treatment and other cancer

indications

– AstraZeneca/MedImmune: sacituzumab govitecan + durvalumab combo in 1st–line mTNBC and mUC – Clovis: sacituzumab govitecan + rucaparib combo in 2nd–line mTNBC and mUC – Yale: monotherapy in endometrial and cervical cancers – Wisconsin: monotherapy in prostate cancer – Preclinical studies in head and neck and prostate cancers

• Launch preparation ongoing, commercial manufacturing on track to meet demand

Building a Blockbuster Brand in Oncology

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Cancer Types Line of Therapy 3rd Line+ 2nd Line 1st Line (Neo)Adjuvant mTNBC mUC Cisplatin-eligible Cisplatin-ineligible ER+ mBC NSCLC

Mono Mono CPI combo Mono/ PARPi combo Mono +PARPi Mono +PARPi

Planned Ongoing Evaluating

CPI combo CPI combo Mono/CPI combo Mono CPI combo Mono

Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer

Low Response Rates in Pre-treated mTNBC*

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Drug Phase N Population ORR (%) PFS (mos) OS (mos)

1st line treatment

Carboplatin1 3 188 1st line 31 3.1 12.4 Docetaxel1 3 188 1st line 36 4.5 12.3 Cisplatin/ Carboplatin2 2 86 1st line (80.2%) 25.6 2.9 11.0

>1st line treatment

Ixabepilone3 2 (pooled analysis) 60 Resistant to anthracycline, cyclophosphamide & taxane or taxane only 6 - 17 1.6 - 2.7

• Capecitabine3

3 (pooled analysis) 208 Prior or resistant to anthracycline & taxane 15 1.7

• Eribulin4

3 (pooled analysis) 199 > 1 prior chemo 11 2.8 12.4

* Includes breast cancer drugs with data from Phase 2/3’s with minimum mTNBC sample size > 60; ORR and PFS data Source of data: 1) Tutt A, SABCS 2014; 2) Isakoff SJ, J Clin Oncol 2015; 3) Perez EA, Breast Can Res Treat 2010; 4) Pivot X, Ann Oncol 2016

Adverse Events (Regardless of Causality)

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• Adverse events were managed with supportive medication or dose modifications

– 25% of patients had dose modifications predominantly to 7.5 mg/kg

• Two patients (1.8%) discontinued due to adverse events (grade 3 transient infusion reaction/grade 2 fatigue)
• There were no treatment-related deaths

Body system Adverse event All grades Grade 3 or 4 Hematologic Neutropenia 63% 41% Febrile neutropenia 8% 7% Anemia 52% 10% Leukopenia 24% 14% Gastrointestinal Nausea 63% 5% Diarrhea 56% 8% Vomiting 46% 5% Constipation 32% 1% Other Fatigue 50% 7% Alopecia 36% NA Decreased appetite 30% 0% Hyperglycemia 23% 4% Hypomagnesemia 21% 1% Hypophosphatemia 15% 8%

Includes all events >20% (all grades) or >5% (grade 3 or 4); NA = not applicable

Sacituzumab Govitecan in Late-Line mTNBC

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108 patients in BLA

• Patients received ≥3rd prior

line for metastatic disease: 100%

• ORR: 33% (local), 32%

(BICR)

• Median DoR: 8.3 months

(local), 6.7 months (BICR)

• Median PFS: 5.5 months

(local)

Percent Reduction in Baseline Target Lesions*

* Two patients did not meet the criteria of two prior therapies for metastatic disease and were not included in the BLA package

Amended ASCENT Phase 3 Study (under SPA): Overview

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National Institutes of Health. https://clinicaltrials.gov/ct2/show/NCT02574455. Accessed March 14, 2018.

• First patient dosed in November 2017 in U.S.
• SPA protocol accepted by EU regulatory authority
• Clinical trial accruing globally

1o Endpoint

• PFS ( BM-)

Sacituzumab govitecan 10 mg/kg IV d1 & 8, every 3 wks Treatment of physician choice

• Capecitabine
• Eribulin
• Gemcitabine
• Vinorelbine

Stratification Factors Continue treatment until progression N = 488

mTNBC (ASCO/CAP)

R/R after ≥2 prior SOC chemo for advanced disease OR 1 therapy for advanced disease who also progressed within 12 months of (neo)adjuvant therapy

• # prior therapies
• Geography
• +/- known BM

(15% cap)

2o Endpoints

• OS (BM-)
• PFS (ITT)
• OS (ITT)

Triple-Negative Breast Cancer

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BLA submitted Phase 3 confirmatory “ASCENT” Potential for CPI or other combo

Planned Ongoing Evaluating

Phase 2 single arm Phase 1/2 PARPi combo

Neoadjuvant Adjuvant

1st Line (10-11k Pts)

2nd Line (9-10k Pts)

3rd Line+ (8-9k Pts)

Stage 3 locally advanced (unresectable), Stage 4 metastatic Stage 1, 2 and 3 (resectable)

Phase 1/2 CPI combo Phase 2 single arm

Sacituzumab Govitecan in Advanced Urothelial Cancer

Low Response Rates in Relapsed / “Refractory” mUC

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Treatment Phase ORR PFS (months) OS (months) Source

Historical ~10% 3 4-9 Vinflunine 3 8.6% 3.0 6.9

Bellmunt J Clin Oncol 2009

Docetaxel 2 8.9% 2.8 9.2

Petrylak D J Clin Oncol 2016

Docetaxel + Ramucirumab 2 24% 5.4 10.4

Petrylak D J Clin Oncol 2016

Docetaxel 3 14% 2.8 Not Reported

Petrylak D Lancet 2017

Docetaxel + Ramucirumab 3 24.5% 4.1 Not Reported

Petrylak D Lancet 2017

Sacituzumab Govitecan in ≥2nd Line mUC

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41 patients enrolled

• Median number of prior

lines: 3 (range, 1‐6)

• ORR: 34% (14/41)

– Prior CPI: 29% (4/14)

• Median duration of

response: 12.6 months (95% CI: 7.5, 12.9)

• Clinical benefit rate

(CR+PR+SD≥6 months): 49%

Percent Reduction in Baseline Target Lesions

• 1 0 0
• 8 0
• 6 0
• 4 0
• 2 0

2 0 4 0 6 0 B e s t R e s p o n se

B e s t % c h a n g e in T L fro m b a s e lin e             

S D P D

 C o m p le te re s p o n s e P a rtia l re s p o n s e S ta b le d is e a s e P r o g r e s s io n

P rio r c h e c k p o in t in h ib ito r T x

72% (26/36) of patients with at least one CT response assessment had reduction of target lesions (sum of diameters)

Tagawa et al, Annals of Oncology (2017) 28 (suppl_5): v295-v329. 10.1093/annonc/mdx371

Cohort 1: N = 100 Cohort 2: N = 40

mUC Phase 2 Pivotal TROPHY U-01 Study Overview

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• Patients will be enrolled across approximately 50 sites in North America and Europe

1o Endpoint

• ORR

(BICR)

Sacituzumab govitecan 10 mg/kg IV d1 & 8, every 3 wks Continue treatment until progression

mUC

Cohort 1: 3rd line post platinum- and PD-1/PD-L1 based therapies

OR

Cohort 2: 2nd line for cisplatin- ineligible patients

2o Endpoints

• DoR
• PFS
• OS

Metastatic Urothelial Cancer

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Planned

TROPHY U-01 Study Phase 1/2 PARPi combo TROPHY U-01 Study

Cisplatin eligible Cisplatin ineligible

Phase 1/2 PARPi combo

1st Line (10-12k Pts)

2nd Line (7-8k Pts)

3rd Line+ (3-4k Pts)

1st Line (8-10k Pts)

2nd Line (6-7k Pts)

3rd Line+ (3-4k Pts)

Ongoing

Phase 1/2 CPI combo

Evaluating

Phase 1/2 CPI combo TROPHY U-01 Study

Sacituzumab Govitecan in ER+/HER2– Metastatic Breast Cancer

Estrogen-Receptor Positive/HER2-Negative mBC

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• Most common form of mBC in the U.S.
• Treatments involve:

– Initially endocrine-based therapies, including CDK 4/6 inhibitors – Subsequently chemotherapy, but response rates to later-line therapies are low

• Poor prognosis for patients with visceral

metastases

• New therapeutic options needed for

treatment-refractory ER+/HER2– mBC

61% 17% 9% 13%

ER+/HER2neg ER+/HER2+ ERneg/HER2+ TNBC

U.S. Stage 4 Breast Cancer Prevalent Population Distribution by Subtype (SEER)

Low Response Rates to Chemotherapy in Pre-Treated mBC

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A: Anthracycline; T: Taxane. *N represents mBC population which includes HER2+ and/or TNBC; ORRs are based on local review. ** TTF

Drug N* Population HR+ % ORR % PFS (months) OS (months) Source Ixabepilone 126 Prior A, T and capecitabine 52 18.3 3.1 8.6 Perez EA JCO 2007 Capecitabine 548 Prior A, T ≤ 3 prior chemo (incl. adjuvant) 47 19.9 4.2 14.5 Kaufman PA JCO 2015 Capecitabine ER+ subgroup 219 Idem 100 NA 5.3 16.8 Twelves C, Breast Cancer Research, 2016 Eribulin ER+ subgroup 198 Idem 100 NA 4.3 18.2 Twelves C, Breast Cancer Research, 2016 Eribulin 508 Prior A and T ≥2 prior chemo 64 13 3.7 13.1 Cortes J Lancet 2010 Vinorelbine 115 Prior A, ≤ 2 lines 51 13 3** 7.5 Jones JCO 1995

Single-Arm, Open-Label Study Design

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Evaluations

• Response by local assessment

(RECIST v1.1)

• Other: safety

Sacituzumab govitecan 10 mg/kg IV d1 & 8, every 3 wks Continue treatment until progression/ unacceptable toxicity ER+/HER2– mBC at last biopsy Key Eligibility Criteria

• Adults, ≥18 years of age
• ECOG: 0-1
• ≥1 prior metastatic therapies
• Measurable disease

Demographics and Patient Characteristics (N=54)

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*Includes lines of therapy given in the (neo)adjuvant setting if patient became metastatic within 12 months (N=4)

**Metastatic sites in >20% patients; 89% (48/54) of patients had liver or lung metastases

Taxane – any setting Anthracycline – any setting 93% 69% CDK 4/6 inhibitors mTOR inhibitors 69% 54% Prior chemotherapy for metastatic disease Fluoropyrimidine agents Taxane Eribulin Platinum agents 80% 57% 33% 24% Sites of metastatic disease at study entry** Bone Liver Chest Lung 80% 82% 37% 31% Female/male, n 54/0 Median age, years (range) 54 (33-79) ECOG performance status 1 Missing 35% 56% 9% Median time from metastatic disease to study entry, years 3.50 ≥ 1 prior chemotherapy line for metastatic disease Median number of metastatic chemotherapy lines Median number of metastatic hormonal therapy lines Median number of prior metastatic treatment lines Hormonal therapy for metastatic disease ≥ 3 lines of hormonal therapy for metastatic disease 98% 2 (0-9)* 3 (1-6)* 5 (2-17)* 100%* 67%*

Adverse Events (Regardless of Causality) All events >20% or Grade 3+ >5%

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** AE frequency based on the available reporting of 50/54 pts. AE data for the remaining 4/54 patients are being collected Body system Adverse event (AE) All grades* Grade 3 or 4* Hematologic Neutropenia Febrile neutropenia Anemia Leukopenia 64% 2% 36% 16% 42% 2% 6% 8% Gastrointestinal Nausea Diarrhea Vomiting Constipation 58% 40% 38% 30% 2% 4% 4% 0% Other Fatigue Alopecia Decreased appetite Cough Alk Phos increase Hypophosphatemia 46% 36% 28% 22% 20% 16% 2% NA 0% 0% 6% 8%

• AEs managed with supportive

medication or dose modifications

– 28% received growth factor support

• 22% of patients had dose reduced to

7.5 mg/kg; 9% occurring in 1st cycle

• Two patients (3.7%) discontinued due to

AEs (grade 3 neutropenia not recovered within 3 weeks; grade 3 diarrhea/ dehydration)

• No treatment-related deaths

• 8 0
• 6 0
• 4 0
• 2 0

2 0 4 0 B e s t R e s p o n s e

(% c h a n g e in ta rg e t le s io n fro m b a s e lin e )

P a rtia l re s p o n s e S ta b le d is e a s e P ro g re s s io n

6 p ts w ith o u t C T a s s e s s m e n t a re n o t s h o w n + C o n tin u in g tre a tm e n t

+ + + + + + + + + + +

Tumor Response to Sacituzumab Govitecan

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• 63% (34/54) of patients with at least
• ne CT response assessment had

reduction of target lesions (sum of diameters)

• Median number of metastatic chemo

lines: 2

• Median number of prior metastatic

lines: 5

Local Response Evaluation by RECIST1.1 Objective response rate CR PR 31% (17/54) 17 Clinical benefit rate (CR+PR+SD ≥6 months) 48% (26/54)

Response Onset and Durability (N=17)

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4 8 1 2 1 6 M o n th s fro m s ta rt o f s a c itu zu m a b g o v ite c an

C o n tin u in g O n s e t o f re s p o n s e // (2 6 .1 ) P rio r C D K 4 /6 in h ib ito r N o p rio r C D K 4 /6 in h ib ito r

• Median duration of response:

7.4 months (95% CI: 4.4, 18.3)

• Median time to onset of response:

2.3 months (range: 1.5-7.8)

• 7 responders were still receiving

sacituzumab govitecan at last assessment

Best response under RECIST 1.1, as per local assessment

Progression-Free Survival (PFS)

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Based on Local Assessment using RECIST 1.1 Median PFS, months (95% CI) 6.8 (4.6, 8.9)

20 40 60 80 100 4 8 12 16 20 24 28 Months Number at risk 49 29 13 3 2 1 1

• 32 patients had objective progression

(maturity = 59%)

• 10 patients are continuing
• 12 other patients censored

– 5 with no CT assessment were censored at baseline – 1 withdrew at 0.7 months after leaving study with AE – The remaining censored pts left study with their last response assessment SD or better

Response to Sacituzumab Govitecan in Subgroups

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**Includes lines of therapy given in the (neo)adjuvant setting if patient became metastatic within 12 months (N=4)

ORR, % (n/N) Onset of metastatic disease from diagnosis < 1 year ≥ 1 year 15% (2/13) 37% (15/41) ≥ 2 prior chemo for metastatic disease* < 2 prior chemo for metastatic disease* 29% (12/41) 38% (5/13) ≥ 3 prior hormonal therapies for metastatic disease* < 3 prior hormonal therapies for metastatic disease* 25% (9/36) 44% (8/18) Prior CDK 4/6 inhibitors No prior CDK 4/6 inhibitors 24% (9/37) 47% (8/17) ORR, % (n/N) Overall 31% (17/54) Age <65 ≥65 29% (12/42) 42% (5/12) Visceral involvement at study entry (Liver/Lung) Yes No 27% (13/48) 67% (4/6) Liver involvement Clinical Benefit Rate in patients with liver involvement (CR+PR+SD ≥6 months) 27% (12/44) 48% (21/44)

ER+/HER2– Breast Cancer

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Stage 3 locally advanced (unresectable), Stage 4 metastatic

Pivotal study

Endocrine & CDK 4/6i Therapy

1st Line Chemo (30-33k Pts)

2nd Line Chemo (26-28k Pts)

3rd Line Chemo (24-26k Pts)

Planned Ongoing Evaluating

Sacituzumab Govitecan in Metastatic Non-Small Cell Lung Cancer

Low Response Rates for Chemotherapy in Previously-Treated mNSCLC

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Treatment Phase

N

ORR PFS (months) OS (months) Source

Docetaxel in 2nd-line Non-squamous 3 290 12% 4.2 9.4 Borghaei et al. N Engl J Med 2015 373:1627-39 Docetaxel in 2nd-line Squamous 3 137 9% 2.8 6.0 Brahmer et al.; N Engl J Med 2015 373:123-135 Docetaxel in 2nd-line PD-L1 ≥ 1% 3 343 9% 4.0 8.5 Herbst et al. Lancet 2016 387(10027):1540-50

Sacituzumab Govitecan in Pretreated mNSCLC

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54 patients enrolled

• Median number of prior

lines: 3 (range, 2‐7)

• ORR: 19% (9/47)

– Prior CPI: 14% (2/14)

• Median duration of

response: 6.0 months (95% CI: 4.8, 8.3)

• Clinical benefit rate

(CR+PR+SD≥6 months): 32%

Percent Reduction in Baseline Target Lesions

Heist et al, Journal of Clinical Oncology 35(24):2790-2797, 2017

• 8 0
• 6 0
• 4 0
• 2 0

2 0 4 0 B est % ch an g e in targ et lesion s fro m b aseline

P a rtia l re s p o n s e (c o n firm e d ) (P R ) U n c o n firm e d P R (P R u ) (s ta b le d is e a s e ) S ta b le d is e a s e P ro g re s s io n 



         

    



S q u a m o u s c e ll h is to lo g y 8 m g /k g s ta rtin g d o s e P rio r c h e c k p o in t in h ib ito r T x  

+ + e a rly C T a s s e s s m e n t a fte r 2 d o s e s

Non-Small Cell Lung Cancer

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Stage 3 locally advanced (unresectable), Stage 4 metastatic

Pivotal study 1st Line Chemo + CPI Combo (100-120k Pts)

2nd Line Chemo (75-85k Pts)

3rd Line Chemo (35-45k Pts)

Planned Ongoing Evaluating

Additional Corporate Information

Sacituzumab govitecan/IMMU-132 (anti-Trop-2-SN-38 ADC)

Metastatic triple-negative breast cancer (FDA granted BTD)

IMMU-140 (anti-HLA-DR-SN-38 ADC) Labetuzumab govitecan/IMMU-130 (anti-CEACAM5-SN-38 ADC)

Metastatic urothelial cancer Pivotal Metastatic colorectal cancer Solid and liquid cancers First-in-Class Antibody-Drug Conjugate (ADC) Programs Other Product Candidates include Epratuzumab, Veltuzumab, Milatuzumab and IMMU-114 for Oncology and Autoimmune Disease Indications

Research/Preclinical Phase 1 Phase 2 Phase 3

Solid tumors IITs

FDA Review

Metastatic ER+/HER2- breast cancer

Broad Pipeline of ADC Therapies

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Registration

BLA

Sufficient Cash Runway to Pursue Strategic Priorities

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Debt (convertible senior notes) $20 Million Basic shares outstanding (fully diluted) 187 (205) Million Cash balance as of 6/30/2018 $639 Million