Seagen to Highlight Preclinical Data for Enfortumab Vedotin and Two Novel Antibody-Drug Conjugates at AACR Annual Meeting

Rhea-AI Summary

Seagen Inc. (NASDAQ: SGEN) announced promising preclinical data on enfortumab vedotin, showing significant antitumor activity and low systemic exposure in non-muscle invasive bladder cancer (NMIBC) models. The study indicated up to 97% tumor growth inhibition and minimal toxicity, supporting the ongoing phase 1 trial (EV-104) for NMIBC patients. Additionally, new data on the novel ADCs SGN-ALPV and SGN-B7H4V highlight their potential across various tumors and an encouraging safety profile. These findings will be presented at the AACR Annual Meeting in New Orleans from April 8-13, 2022.

Positive

• Enfortumab vedotin showed 97% tumor growth inhibition in preclinical NMIBC models.
• Minimal systemic toxicity and encouraging safety profile for enfortumab vedotin.
• New ADCs SGN-ALPV and SGN-B7H4V demonstrated robust antitumor activity in preclinical studies.
• Initiation of EV-104 phase 1 trial in NMIBC patients based on strong preclinical results.

Negative

• None.

--Intravesical enfortumab vedotin demonstrated antitumor activity and limited systemic exposure in preclinical models of non-muscle invasive bladder cancer--

--Antibody specificity, antitumor activity and safety profile of SGN-ALPV in preclinical models provide basis for the first-in-human phase 1 clinical study--

BOTHELL, Wash.--(BUSINESS WIRE)-- Seagen Inc. (Nasdaq: SGEN) today announced data from intravesical instillation of enfortumab vedotin (EV) in a non-muscle invasive bladder cancer (NMIBC) preclinical model in addition to preclinical data from SGN-ALPV and SGN-B7H4V, two of its novel antibody-drug conjugates (ADCs) that utilize the company’s proprietary vedotin drug linker technology. These data will be presented at the American Association for Cancer Research (AACR) Annual Meeting, taking place in New Orleans, April 8-13, 2022. Seagen and Astellas Pharma Inc. are co-developing enfortumab vedotin under a 50:50 worldwide development and commercialization collaboration.

“We are encouraged by the preclinical intravesical EV data showing limited systemic exposure and antitumor activity with an encouraging safety profile. These data served as the basis for initiating the ongoing phase 1 trial in patients with NMIBC,” said Scott Peterson, Ph.D., Senior Vice President of Research at Seagen. “Additionally, preclinical data presented from SGN-ALPV suggest it may have applications across several tumor types and adds to our broad pipeline of novel ADCs.”

Highlights of Seagen Programs Presented at AACR

Enfortumab Vedotin

Enfortumab vedotin demonstrated antitumor activity in preclinical models of non-muscle invasive bladder cancer (NMIBC). Enfortumab vedotin is directed to Nectin-4, which is highly prevalent in NMIBC. Studies with human bladder cancer cells expressing Nectin-4 showed sustained activity under conditions mimicking intravesical dosing and achieved tumor growth inhibition of 97% when administered in an orthotopic xenograft animal model of NMIBC. Intravesical administration of enfortumab vedotin was well tolerated in a good laboratory practice (GLP) study with minimal local and no systemic toxicities at doses up to six-fold the intravenous maximum tolerated dose.

The antitumor activity and safety profile seen in these preclinical studies support further investigation of intravesical enfortumab vedotin in this patient population, which is now enrolling in a phase 1 trial, EV-104.

SGN-ALPV

SGN-ALPV is a novel ADC designed to target two proteins, ALPP and ALPPL2, to maximize drug delivery. ALPP and ALPPL2 are aberrantly co-expressed in a broad set of solid tumors, including ovarian, endometrial and germ cell cancers. In preclinical studies, SGN-ALPV exhibited robust antitumor activity in cell line and patient-derived xenograft cancer models with both homogenous and heterogeneous expression of placental alkaline phosphatases ALPP and ALPPL2, consistent with robust monomethyl auristatin E (MMAE)-directed cytotoxicity and bystander activity of vedotin ADCs.

Importantly, ALPP and ALPPL2 exhibit a highly restricted normal tissue expression, which may enable a favorable safety profile. Differential expression of ALPP and ALPPL2 in the tumor versus normal tissue, antibody specificity, antitumor activity and tolerability of SGN-ALPV provided a strong rationale for the initiation of the first-in-human phase 1 clinical study currently enrolling patients.

Details of Seagen Presentations at AACR Annual Meeting 2022:

Abstract Title	Abstract #	Presentation	Presenter
Enfortumab vedotin, a Nectin-4 directed ADC, demonstrates compelling tolerability and anti-tumor activity with intravesical instillation in preclinical models of non-muscle invasive bladder cancer	#1140	Poster session: PO.ET05.02-Preclinical and Clinical Pharmacology, Section 25 April 11 9:00 a.m. – 12:30 p.m. ET	C. Carosino
SGN-B7H4V shows immunomodulatory activity through induction of immunogenic cell death	#1281	Poster session: PO.CL06.04-Immune Mechanisms Invoked by Other Therapies, Section 32 April 11 9:00 a.m. – 12:30 p.m. ET	E. Gray
SGN-ALPV a novel, investigational vedotin ADC demonstrates highly effective targeting of oncofetal phosphatases ALPP and ALPPL2 in preclinical models	#1766	Poster Session: PO.ET01.04- Antibody-Drug Conjugates, Section 21 April 11 1:30 p.m. – 5:00 p.m. ET	S. Anderson

About Enfortumab Vedotin

Enfortumab vedotin-ejfv (PADCEV^®) is an antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.^i,ii Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).

About SGN-ALPV

SGN-ALPV is a novel, investigational vedotin antibody drug conjugate (ADC) designed to bind and internalize the homodimers (ALPP or ALPPL2) or heterodimers (ALPP/ALPPL2-ADC) complex from the surface of tumor cells and release the microtubule-disrupting agent MMAE, inducing cell cycle arrest and apoptosis. SGN-ALPV has demonstrated highly effective targeting of alkaline phosphatases ALPP and ALPPL2 in preclinical models and will be initially evaluated in ovarian and endometrial cancer, non-small cell lung cancer (NSCLC), gastric cancer, cervical cancer, testicular germ cell tumors and ovarian germ cell tumors where ALPP and ALPPL2 are highly prevalent.

About SGN-B7H4V

SGN-B7H4V is a novel, investigational vedotin ADC directed to the T cell checkpoint ligand, B7-H4. B7-H4 expression is limited on normal tissue and overexpressed on a variety of solid malignancies, including breast, ovarian and endometrial tumors. SGN-B7H4V is designed to bind and internalize the B7-H4/ADC complex from the surface of the tumor cells and release the therapeutic payload MMAE, inducing MMAE-mediated direct cytotoxicity, bystander killing and immunogenic cell death, as well as antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). SGN-B7H4V demonstrates strong activity in xenograft models, including models with heterogenous B7-H4 expression.

About Seagen

Seagen is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people’s lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.

Forward-looking Statements

Certain statements made in this press release are forward-looking, such as those, among others, relating to ongoing or planned clinical trials; clinical development plans; and the therapeutic potential of SGN-ALPV, enfortumab vedotin and SGN-B7H4V, including their possible efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include, without limitation, the possibility that ongoing and subsequent clinical trials may fail to establish sufficient efficacy; that adverse events or safety signals may occur; that adverse regulatory actions or other setbacks could occur in clinical trials even after promising results in earlier clinical trials or preclinical studies; that setbacks in development could occur as a result of the difficulty and uncertainty of pharmaceutical product development; and other factors. More information about the risks and uncertainties faced by Seagen is contained under the caption “Risk Factors” included in the company’s Annual Report on Form 10-K for the year ended December 31, 2021 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

ⁱ PADCEV [package insert]. Northbrook, Ill.: Astellas Pharma US, Inc.

ⁱⁱ Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res. 2016;76(10):3003-13.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220408005364/en/

For Media

David Caouette

Vice President, Corporate Communications

(310) 430-3476

dcaouette@seagen.com

For Investors

Peggy Pinkston

Senior Vice President, Investor Relations

(425) 527-4160

ppinkston@seagen.com

Source: Seagen Inc.

FAQ

What were the results of enfortumab vedotin in preclinical models?

Enfortumab vedotin demonstrated up to 97% tumor growth inhibition with minimal systemic toxicity in NMIBC preclinical models.

What is the purpose of the EV-104 clinical trial?

The EV-104 trial aims to evaluate the safety and efficacy of enfortumab vedotin in patients with non-muscle invasive bladder cancer.

What are SGN-ALPV and SGN-B7H4V?

SGN-ALPV and SGN-B7H4V are novel antibody-drug conjugates developed by Seagen, showing robust antitumor activity in various preclinical cancer models.

When will the data from Seagen be presented?

The data will be presented at the AACR Annual Meeting taking place in New Orleans from April 8-13, 2022.

What is the significance of the AACR Annual Meeting presentation?

The AACR Annual Meeting presentation will showcase Seagen's advancements in cancer therapies, crucial for attracting investor interest and validating their development pipeline.