**South San Francisco, CA – November 10, 2022** – PACT Pharma, Inc., a privately held biopharmaceutical company developing transformational personalized neoantigen-specific and off-the-shelf T cell receptor (TCR)-T cell therapies for the eradication of solid tumors, today reported data from the first clinical study using CRISPR gene editing technology to substitute a gene in patients’ immune cells to treat cancer. Results from the study, which was conducted with collaborators at nine academic centers using PACT’s proprietary platforms, demonstrated early proof-of-concept that a patient’s immune system can be reprogrammed to recognize their own cancer. The study findings were the focus of a late breaking oral presentation at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2022), as well as a peer-reviewed paper in Nature that was published in conjunction with SITC 2022.


Every patient’s immune system contains T cells that can utilize specific receptors to find and kill
cancer cells. Unfortunately,
patients often do not have
enough of these T cells to mount a complete
and effective attack on their cancer. PACT has developed proprietary technology platforms
capable of creating
engineered tumor-specific TCR-T cell therapies
this unmet treatment need. This is accomplished by isolating TCRs directly from the blood of
with the potential to address
patients and then using
CRISPR gene editing to engineer those isolated TCRs back into the patients’ own T cells. Once infused back into the patient, these engineered T cells redirect the
patients’ immune system to recognize the patient’s own cancer.

As part of the oral presentation at SITC, researchers reported findings from a Phase 1 study in which 16 patients with solid tumors including colon, breast and lung cancer, were treated with their redirected T cells.
targeting mutations related to each patient’s cancer.
and up to three TCRs were selected for each patient as a basis for their individual therapy. The selected TCRs were CRISPR engineered to replace the existing TCR with a cancer-specific one. These T cells were expanded to large numbers and then, up to three TCR cell products were infused back into each
patient following a course of conditioning chemotherapy.
isolate T cells
The study involved researchers using patients’ blood samples to directly
 These T cells were then
  sequenced, leading to the identification of 175 unique, cancer specific TCRs
 
The gene edited T cells preferentially trafficked to the tumor and could be recovered from post- infusion biopsies in all patients where biopsies were available. Of note, the CRISPR-edited T cells frequently represented the top 2-20% of immune cells in the tumor and led to tumor size reduction in some lesions of a patient with lung cancer. Patients showed expected side effects caused by conditioning chemotherapy and two patients had potential side effects from the gene edited cells, one with fevers and chills and the other with confusion, both recovering promptly. The study findings demonstrated the PACT therapy to be well tolerated while showing encouraging initial signs of clinical activity.

  “This study represents a significant leap forward in efforts to develop a personalized treatment for cancer that utilizes isolated immune receptors that can specifically recognize mutations within a patient’s own cancer,” said Antoni Ribas, M.D., Ph.D., professor of medicine and surgery at the University of California, Los Angeles, and a corresponding author of the Nature paper. “This important research was only made possible with several next generation technology platforms developed by the PACT team. Particularly critical to this effort was the newly developed ability to use CRISPR to replace immune receptors in clinical grade cell preparations in a single step. The work highlighted at SITC and within the Nature paper paves the way for the continued advancement of research aimed at delivering safe and effective, patient specific TCR T cell
 therapies for the treatment of cancer.”

 This groundbreaking clinical study offers early proof-of-concept for several cutting-edge steps of the PACT approach to reprogramming a patient’s immune system to recognize and defeat their cancer, including:
- Isolating and cloning multiple TCRs from blood that recognize patient specific mutational neoantigens
- Utilizing single-step, non-viral precision gene editing with CRISPR to simultaneously knock-out endogenous TCRs and knock-in patient-specific TCRs
- Manufacturing clinical grade TCR engineered T cells with a defined composition of up to three TCRs
- Safely infusing up to three different gene edited TCR T cell products
- Demonstrating the ability of the infused transgenic T cell products to traffic to patient tumors

“We are thrilled to share the findings from this first-in-human clinical trial which met its primary endpoints, demonstrating both the tolerability and feasibility of TCR discovery and manufacturing of a multi-TCR product using complete non-viral gene editing and safety of the infusion of a three TCR product,” said Stefanie Mandl, Ph.D., chief scientific officer, PACT Pharma. “We look forward to continuing our research and development efforts in this area as we work to make personalized TCR T cell therapies a reality for all cancer patients. A key element to achieving this goal of broad applicability is our proprietary catalogue of 64 human leukocyte antigens (HLAs), which cover patients of all ethnicities. This is a key differentiator from most current TCR T cell therapies that are limited to only a single HLA molecule that is common in Caucasians.”

It is important to note that previous CRISPR-related clinical trials have involved deleting (knocking-out) specific genes to drive immune system activation against cancer or, more recently, inserting (knocking-in) an artificial receptor to guide cancer cell recognition. However, these studies have not combined knocking-out endogenous genes and replacing them with the insertion (knocking-in) of substitute genes isolated from the same patient. In that regard, this PACT clinical trial represents a first-of-its-kind scientific breakthrough.

A copy of the poster affiliated with the oral presentation at the SITC conference is available on the “Events” page of the PACT Pharma website at: [https://www.pactpharma.com/news/?filter=events](https://www.pactpharma.com/news/?filter=events).
  
A copy of the newly published Nature article, entitled, “Non-viral precision T cell receptor replacement for personalized cell therapy,” can be accessed at:
[https://www.nature.com/articles/s41586-022-05531-1.](https://www.nature.com/articles/s41586-022-05531-1)


**About PACT Pharma, Inc.**
PACT is a privately held biopharmaceutical company pioneering individualized and off-the-shelf, non-viral precision genome engineered, tumor-specific TCR T cell therapies for the treatment of patients with solid cancers. 

For more information, please visit www.pactpharma.com.

**Contacts**:

PACT Pharma
Atulya R. Agarwal 
aagarwal@pactpharma.com

Vida Strategic Partners (on behalf of PACT Pharma)
Tim Brons (Media)
415-675-7402
tbrons@vidasp.com

PACT Pharma Reports Data From First Clinical Study Using CRISPR to Substitute a Gene in Patients’ Immune Cells to Treat Cancer

Press Releases

Details of the company’s presentations at SITC 2022 are as follows:

**Late Breaking Oral Presentation #1478 (With Accompanying Poster):**
- *Title*: A Phase I Study of Personalized Adoptive TCR T Cell Therapy in Patients with Solid Tumors: Safety, Efficacy, and T Cell Trafficking to Tumors of Non-virally Gene Edited T Cells
- *Presenting Author*: Stefanie Mandl, Ph.D., chief scientific officer, PACT Pharma
- *Category/Session*: Late Breaking Abstract Session 103
- *Date/Time*:  Thursday, November 10, 2022, 11:10 a.m. – 11:40 a.m. Eastern
- *Location*:  Hall B2

**Oral Presentation #123**:

- *Title*: Landscape Analysis of the Neoepitope-specific T Cell Responses in Patients with and without Clinical Benefit from Immune Checkpoint Blockade Therapy 
- *Presenting Author*: Cristina Puig Saus, Ph.D., adjunct assistant professor, University of California, Los Angeles
- *Category/Session*: Rapid Oral Abstracts – Basic Science Session 104
- *Date/Time*:  Thursday, November 10, 2022, 12:25 – 12:33 p.m. Eastern
- *Location*:  253ABC


**Poster Presentation #320**:

- *Title*: Rapid Identification of a TCR Library Targeting the HPV E6/E7 Oncoproteins to Enable Multi-TCR T-Cell Therapies for Patients with HPV16+ Epithelial Cancers
- *Presenting Author*: Stefanie Mandl, Ph.D., chief scientific officer, PACT Pharma
- *Category/Session*: Cellular Therapies Poster Session
- *Date*:  Friday, November 11, 2022
- *Location*:  Poster Hall C


**Poster Presentation #712**:

- *Title*: Retrospective Tumor Microenvironment Analysis from a Personalized neoTCR-T Cell Therapy Clinical Trial and Its Potential Applications for Off-the-Shelf HPV TCR T Cell therapies
- *Presenting Author*: Chad Smith, Ph.D., associate director, bioinformatics, PACT Pharma
- *Category/Session*: Clinical Trials in Progress Poster Session
- *Date*:  Friday, November 11, 2022
- *Location*:  Poster Hall C


Additional information on the 37th Annual Meeting of SITC is available through the conference website at: https://www.sitcancer.org/2022/home


**About PACT Pharma, Inc.**
PACT is a privately held biopharmaceutical company pioneering individualized and off-the-shelf, non-viral precision genome engineered, tumor-specific TCR T cell therapies for the treatment of patients with solid cancers. 

For more information, please visit www.pactpharma.com.

**Contacts**:

PACT Pharma
Atulya R. Agarwal 
aagarwal@pactpharma.com

Vida Strategic Partners (on behalf of PACT Pharma)
Tim Brons (Media)
415-675-7402
tbrons@vidasp.com


PACT Pharma to Present New Data Highlighting First-of-its-Kind Personalized Neoantigen TCR T Cell Therapy Platform at SITC 2022

PACT is a privately held immuno-oncology company dedicated to engineering T cell therapies by seeking to harness the inherent biology and curative potential of each patient's immune system to treat their cancer and advance the field of immune-driven medicines.

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