PF-08046049 / Pfizer, Palvella Therapeutics - LARVOL DELTA

SGNBB228-001: A Study of PF-08046049/SGN-BB228 in Advanced Melanoma and Other Solid Tumors (clinicaltrials.gov) - P1 | N=41 | Active, not recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Dec 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Colorectal Cancer • Cutaneous Melanoma • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRAF

PF-08046049 synergizes with checkpoint inhibitors to drive CD8+ T cell effector differentiation and tumor clearance in an IO-resistant model (AACR 2025) - "Additionally, while the combination therapy of anti-CTLA-4 and anti-PD-1 (Ipilimumab-Nivolumab) improves response rate and overall survival compared to monotherapies, it also leads to increased toxicity and immune-related adverse events...However, nontargeted 4-1BB signaling poses a risk of widespread peripheral immune activation and liver toxicity, as was the case for the 4-1BB agonist Urelumab...We found that while anti-PD-1 and anti-CTLA-4 can target and expand stem-like CD8+ T cells in both the tumor-draining lymph node and TME, BB228 is able to drive the differentiation of those stem-like cells into effectors, resulting in tumor killing. These data illustrate that BB228 has a distinct and complementary mechanism of action from the current melanoma SOC treatments."

Checkpoint inhibition • Melanoma • Oncology • Solid Tumor • CD8 • MELTF • MELTF

SGNBB228-001: A Study of PF-08046049/SGN-BB228 in Advanced Melanoma and Other Solid Tumors (clinicaltrials.gov) - P1 | N=41 | Active, not recruiting | Sponsor: Seagen, a wholly owned subsidiary of Pfizer | Recruiting ➔ Active, not recruiting | N=275 ➔ 41 | Trial completion date: Apr 2028 ➔ Oct 2025 | Trial primary completion date: Apr 2027 ➔ Sep 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Colorectal Cancer • Cutaneous Melanoma • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRAF

SGNBB228-001: A Study of PF-08046049/SGN-BB228 in Advanced Melanoma and Other Solid Tumors (clinicaltrials.gov) - P1 | N=275 | Recruiting | Sponsor: Seagen Inc. | Trial completion date: Nov 2027 ➔ Apr 2028 | Trial primary completion date: Nov 2026 ➔ Apr 2027

Trial completion date • Trial primary completion date • Colorectal Cancer • Cutaneous Melanoma • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRAF

Phase I study of the investigational CD228 x 4-1BB costimulatory antibody anticalin bispecific SGN-BB228 (PF-08046049) in advanced melanoma and other solid tumors (ESMO 2024) - P1 | "Enrolment is ongoing in the US, Canada and Europe. NCT05571839."

Metastases • P1 data • Cutaneous Melanoma • Eye Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Uveal Melanoma • BRAF • MELTF • MELTF

SGNBB228-001: A Study of PF-08046049/SGN-BB228 in Advanced Melanoma and Other Solid Tumors (clinicaltrials.gov) - P1 | N=275 | Recruiting | Sponsor: Seagen Inc. | Trial completion date: Sep 2028 ➔ Nov 2027 | Trial primary completion date: Oct 2025 ➔ Nov 2026

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRAF

Phase 1 study of SGN-BB228, an investigational CD228 x 4-1BB costimulatory antibody anticalin bispecific, in patients with advanced melanoma and other solid tumors (SGNBB228-001). (ASCO 2023) - P1 | "Enrollment is ongoing in the US and planned in Europe. Clinical trial information: NCT05571839."

Clinical • Metastases • P1 data • Colorectal Cancer • Cutaneous Melanoma • Immune Modulation • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRAF • MELTF • MFI2

Seagen to Highlight Data From Oncology Portfolio and Pipeline at the 2023 American Society of Clinical Oncology Annual Meeting (Businesswire) - "Updated Phase 1 data will be presented for SGN-B6A, a wholly-owned, first-in-class vedotin ADC directed to integrin beta-6, a novel target that is highly expressed in multiple solid tumors....Additionally, initial data will be presented from studies evaluating Seagen’s approved medicines in potential new cancer types. Data from a Phase 2 basket study of TUKYSA® (tucatinib) and trastuzumab in previously treated HER2-positive metastatic biliary tract cancer will be featured in an oral presentation on Friday, June 2."

Clinical data • P1 data • P2 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

SGN-BB228, a CD228-directed costimulatory antibody anticalin® bispecific provides potent and conditional 4-1BB costimulation to T cells in vivo and in an in vitro model of T cell exhaustion (AACR 2023) - P1 | "Interestingly, in this system, anti-PD-1 (nivolumab) failed to reinvigorate functionally exhausted T cells despite high PD-L1 expression by tumor cells. Together these data highlight SGN-BB228, a first-in-class, investigational CD228 x 4-1BB costimulatory Antibody Anticalin® bispecific with potent and CD228-conditional 4-1BB costimulatory activity with therapeutic potential in multiple solid tumor types. These data support the first-in-human phase 1 clinical trial of SGN-BB228 in advanced melanoma and other solid tumors (NCT05571839), which is currently recruiting."

IO biomarker • Preclinical • Lung Cancer • Melanoma • Mesothelioma • Oncology • Solid Tumor • MELTF • MFI2 • PD-L1 • TNFRSF9

Pieris Pharmaceuticals Announces $5 Million Milestone from Seagen for Initiation of Phase 1 Trial of CD228 x 4-1BB Bispecific Molecule (Mabcalin SGN-BB228 (PRS-346) (Yahoo Finance) - "Pieris Pharmaceuticals, Inc....announced that the Company has achieved a $5 million milestone from Seagen. The milestone is based on dosing the first patient in a Seagen-sponsored phase 1 study of SGN-BB228 (PRS-346), a novel bispecific antibody-Anticalin molecule (Mabcalin) that is designed to provide a potent costimulatory bridge between tumor-specific T cells and CD228 expressing tumor cells. The Seagen-sponsored (NCT05571839) open-label phase 1 study is evaluating the safety and tolerability of SGN-BB228 in patients with advanced melanoma and other solid tumors. This program is one of three ongoing immuno-oncology programs with Seagen and preclinical data were recently presented at the Society for Immunotherapy of Cancer's (SITC) Annual Meeting in Boston. Pieris has an opt-in option to a U.S. co-promotion for one program in the collaboration."

Financing • Melanoma • Oncology • Skin Cancer • Solid Tumor

Seagen to Highlight New Research from its Diverse Pipeline of Targeted Cancer Therapy Candidates at the Society for Immunotherapy of Cancer’s (SITC) Annual Meeting (Businesswire) - "Seagen...announced that data from the company’s diverse pipeline of targeted cancer therapy candidates will be presented at the Society for Immunotherapy of Cancer’s (SITC) Annual Meeting being held November 8-12 in Boston....'We are also sharing new data demonstrating enhanced preclinical activity of enfortumab vedotin in combination with immune checkpoint inhibitors, as well as preclinical data that support the initiation of a first-in-human study of a bispecific molecule called SGN-BB228'."

Preclinical • Oncology

SGN-BB228 is a first-in-class CD228-targeted costimulatory Antibody Anticalin bispecific delivering potent and conditional 4-1BB costimulation to tumor-specific T cells (SITC 2022) - "Conclusions Together these data introduce SGN-BB228, a first-in-class, investigational CD228/4-1BB costimulatory Antibody Anticalin® bispecific with potent and CD228-conditional 4-1BB costimulatory activity with therapeutic potential in multiple solid tumor types. These data support future clinical study of SGN-BB228 in a first-in-human Phase 1 trial."

IO biomarker • Lung Cancer • Melanoma • Mesothelioma • Oncology • Solid Tumor • MFI2 • TNFRSF9

Seagen Reports Third Quarter 2022 Financial Results (Businesswire) - "TUKYSA in Combination with Trastuzumab Granted Priority Review by FDA for Previously Treated HER2-Positive Metastatic Colorectal Cancer...The sNDA submission is based on the results of the pivotal phase 2 MOUNTAINEER trial and the FDA target action date is January 19, 2023....Seagen will present preclinical research from several other early-stage programs, including SGN-BB228, an Anticalin®-based bispecific antibody. The SITC Annual Meeting is taking place November 8-12, 2022."

PDUFA date • Preclinical • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of SGN-BB228 in Advanced Melanoma and Other Solid Tumors (clinicaltrials.gov) - P1 | N=275 | Recruiting | Sponsor: Seagen Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRAF

Pieris Pharmaceuticals Reports Third Quarter 2022 Financial Results and Provides Corporate Update (Pieris Press Release) - "The investigational new drug (IND) application for the phase 1 study of SGN-BB228...has been accepted. Seagen plans to initiate a phase 1 study for SGN-BB228 in the coming months, for which Pieris will receive a milestone payment. Seagen will also present preclinical data for the program at a poster session during the Society for Immunotherapy of Cancer 37^th Annual Meeting."

IND • New P1 trial • Preclinical • Oncology

A Study of SGN-BB228 in Advanced Melanoma and Other Solid Tumors (clinicaltrials.gov) - P1 | N=275 | Not yet recruiting | Sponsor: Seagen Inc.

New P1 trial • Colorectal Cancer • Cutaneous Melanoma • Gastrointestinal Cancer • Lung Cancer • Melanoma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRAF