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Evolution of Antibody-Based Drugs for Cancer

Naked mAbs

The exception, not the rule: while a few highly effective drugs exist, such as Rituxan, Herceptin, and Avastin, the vast majority are inactive.
Lack of a platform: Most naked mAbs fail to achieve efficacy.

Challenge: ACTIVITY

Binding to cancer cells alone is insufficient to cause the destruction of cells.

Antibody-Drug Conjugates (ADCs)

Limited success rate: fifteen approved out of hundreds evaluated.
Efficacy bottleneck: requires tumors with high target antigen expression. Poor endocytosis results in minimal payload accumulation inside cancer cells.

Challenge: SAFETY

Systemic toxicity of the payload limits dosing.

Immuvia's Cancerlysin™

Bispecific Antibodies

Mechanism of action: First module targets a tumor specific antigen, while a second module triggers apoptosis (programmed cell death). Cancerlysins™ work by activating a signaling pathway, a more potent and a safer mechanism than ADCs or conventional chemotherapeutics.
Enhanced Safety Profile: Payload-free design eliminates the risk of dose-limiting systemic toxicity. Our flagship drug candidate proved to be non-toxic in a non-human-primate study at 5-10x anticipated therapeutic dose.
Superior Antitumor Efficacy at a safe dose: Enhanced tumor-killing ability compared to conventional therapies. Single agent activity in broad range of tumors. Robust anti-tumor activity seen across multiple tumor models.

IMV-M™ anti-tumor activity as a single agent with a single injection at a safe dose across multiple tumor models is significantly superior to prior therapies

DISCOVERY
IN-VITRO
VALIDATION
IN-VIVO
VALIDATION
CMC-READY

IMV-M™NSCLC, Gynecologic & Pancreatic

Powerful

Pancreatic Adenocarcinoma

5 mg/kg dose - robust activity

Three out of five mice are tumor-free at the end of the study
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Non-targeting/apopt. machinery targeting BSAb
IMV-M™

Dose Dependent

Pancreatic Adenocarcinoma

Evidence of dose-dependent effect

Tumor growth in individual mice
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1 mg/kg
2.5 mg/kg
5 mg/kg

Robust

Lung Adenocarcinoma

5 mg/kg dose - Robust activity

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Non-targeting Ab/anti-DR5
Anti-MUC16 antibody
IMV-M

IMV-M™ is selective, killing only targeted cells demonstrating superior safety unattainable via traditional ADC approaches

Side-by-side xenograft models proving selectivity and safety: MUC16-positive vs normal tissue proxy

Effective on Target, High MCU16

MUC16-positive xenografts (Targeted)

3 out of 4 mice - cured

1 out of 4 mice - prolonged remission

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IMV-M™

Safe off Target, No MUC16

MUC16-negative xenografts (Not Targeted)

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IMV-M™

IMV-M™ is not toxic in non-human primate study

Antigen Cross-Reactivity

Both the anti-MUC16 and anti-DR5 components of IMV-M™ cross-react with the respective cynomolgus monkey antigens*, indicating that this species is a suitable preclinical model for evaluating the systemic toxicity of IMV-M™

Zero Adverse Effects

IMV-M™ showed no adverse effects in treated animals up to at least 20 mg/kg, with multiple doses, while the effective human therapeutic dose is expected to be ~3 mg/kg

Zero Hepatotoxicity

All clinical chemistry and hematology parameters remained within normal range, including lack of liver enzymes elevation at all time points, indicating lack of hepatotoxicity (see addendum)

*[US Patent 7723485; DOI: 10.1158/0008-5472.CAN-06-4512; DOI: 10.1158/1535-7163.MCT-20-0253]

Expected therapeutic dose in humans: ~3 mg/kg

ImmuVia overcomes limitations of prior MUC16-targeted therapies via novel Mechanism of Action

MUC16

Established and validated target

Absent in most normal tissues

Binding to MUC16 alone does not kill MUC16-positive cells

ADC DMU46064A targeting MUC16

Modest preclinical activity (and only active in cancer cells with an extremely high MUC16 expression)

Promising activity in Phase 1 trials (ORR 41% at doses of 3.2 to 5.6 mg/kg)

Discontinued due to their narrow therapeutic window driven by payload toxicity.

No MUC16-related systemic toxicity, validating the safety of the antibody targeting MUC16.

The history of MUC16 targeting highlights the need for a large therapeutic window via new generation of ADC-mimetic molecules not constrained by payload toxicity.

IMV-M™'s MoA ensures Broad Therapeutic Window

Payload is non-toxic

Preclinical activity is robust

Preclinical efficacy even in moderate MUC16 expressors

MoA is more powerful: activation of a signaling pathway vs cell intoxication

ImmuVia overcomes limitations of prior DR5-targeted therapies via novel Mechanism of Action

Recent discontinued anti-DR5 drug candidates

Eftozanermin α, Aplitabart, RG738634, BI 90571135

Modest preclinical activity

Marginal clinical activity

Recent anti-DR5 drug candidates

Aponermin

Modest preclinical activity

Approved in China; limited activity, in combination

Ozekibart

Modest preclinical activity

Currently in Ph2; limited activity, in combination

Prior attempts at DR5 targeting inform the need for a drug capable of super-clustering DR5 on tumor cells, and only in tumor cells, to create meaningful clinical impact.

IMV-M™ is the first and only therapeutic in development that is designed and proven to super-cluster DR5 on targeted cells triggering apoptosis.