About
PHASE ONE

Letter from the
Board Chair

Medical
Grants

Community
Grants

Cancer Research
Q&A

Thank
You

$24M
INVESTED

52
GRANTS FUNDED

24
CANCER TYPES

Letter from the Board Chair

As we reflect on another remarkable year at PHASE ONE, I want to extend my heartfelt gratitude for your steadfast support and generosity.

Last year, our fundraising efforts reached new heights with our Annual Gala raising over $1 million and our 3rd Annual FACT for PHASE ONE Pickleball Social bringing in an additional $251,000. Your enthusiasm and commitment to these events directly contribute to our ability to find and fund life-saving cancer research, and for that we could not be more grateful.

Over the course of the year, we helped three visionary doctors kickstart their Phase I + II clinical trials. Those are now well underway, bringing our total number of active trials funded by PHASE ONE to 13. Each one connecting cancer patients to potentially life-saving treatments– and it’s all possible because of YOU.

2023 also saw PHASE ONE fund its 50th grant for cancer research since our founding in 1999. This milestone underscores the unwavering support and relentless determination of the PHASE ONE community to make a meaningful mark on cancer care.

I invite you to dive deeper into our Annual Report to see the full scope of your impact. Inside, you will find detailed accounts of the groundbreaking research we support, updates from previous grantees, and more.

Thank you for being an integral part of the PHASE ONE community. We look towards the future with optimism and hope, knowing that there are many more life-saving treatments on the horizon. We are so grateful to have you as a partner on this journey.

Metastatic ER-positive, HER2-negative breast cancer is a type of breast cancer that has spread to other parts of the body and is characterized by the presence of estrogen receptors (ER) and the absence of human epidermal growth factor receptor 2 (HER2) receptors.

Approximately 13% of women born in the US today will develop breast cancer, and of those, ~80% are estrogen receptor-positive.

While there are various FDA-approved treatment options available, oncologists lack an approved biomarker to determine which treatment will be most effective for each individual patient in second-line treatment for these metastatic breast tumors.

To address this critical need, Dr. Nath in collaboration with Dr. Andrea Bild at City of Hope and Dr. Rachel Layman at MD Anderson Cancer Center have developed an innovative and cutting-edge systems biology biomarker approach that leverages genomic data and an artificial intelligence algorithm.

By analyzing the unique characteristics of each patient's tumor, their approach guides oncologists in selecting the most suitable treatment for optimal patient care.

Their novel biomarker, known as "ENDORSE," leverages the transcriptome of patient tumors to predict endocrine therapy response, and has demonstrated superior and consistent performance over clinical covariates and multiple published signatures. By incorporating ENDORSE and a new biomarker for mTOR inhibitor response, they aim to improve patient outcomes in terms of progression-free survival.

This trial represents a groundbreaking advancement as it steers breast cancer patients toward the most optimal treatment option after initial therapy no longer yields satisfactory results using sophisticated computational methods.

By collecting and analyzing pre- and post-treatment tumor samples, the team also aims to identify emerging drug targets within progressing tumors. This valuable information will contribute to the continued targeting of cancer cells, even in the metastatic setting, with the goal of achieving durable responses to treatment.

The AIM4 trial is a partnership with City of Hope and MD Anderson Cancer Center and will also collaborate with Inova Health System and Cleveland Clinic.

Approximately 1 in 285 children in the U.S. will be diagnosed with cancer before their 20th birthday. Most of these cancers originate from solid organs or soft tissues, primarily the brain or extracranial sites.

While advancements in therapies have improved survival rates, treating advanced cases, especially those that have spread, remains challenging and treatment is often associated with long-term toxicities.

Immunotherapy, a preferred alternative to standard chemotherapy, has shown promise in adults but has not had much success in children with relapsed or refractory solid tumors.

Dr. O’Neill is investigating a potential breakthrough treatment involving a new antibody called 2141-V11. This antibody aims to activate immune cells within pediatric solid tumors and enhance the body's natural defenses against cancer by targeting a receptor called CD40, found on various immune cells, that can activate the immune cells to better recognize cancer cells directly and stimulate T cell responses.

The primary goal of this study is to evaluate the safety and effectiveness of delivering this antibody directly into the tumor (intratumoral injection) for pediatric patients with solid tumors.

This innovative approach holds promise due to its potential to activate immune cells within the tumor microenvironment, which might overcome the challenges posed by low tumor immunogenicity (ability to provoke an immune response) commonly observed in pediatric cancers — potentially revolutionizing our understanding of treating solid tumors in children.

The direct delivery of this antibody into the tumor compartment will provide an unparalleled platform for tissue collection supporting translational, longitudinal research studies— allowing researchers to investigate and potentially identify biomarkers associated with effective anti-tumor immunity in children.

The results from this study are poised to fill a critical gap in what we know about how the immune system fights cancer in children, and if successful, could pave the way for a new era of targeted therapies that harness the power of the immune system, offering renewed hope for young patients and their families.

T-ALL is an aggressive type of Acute Lymphoblastic Leukemia (ALL) that affects the lymphoid-cell-producing stem cells, particularly a type of white blood cell called T lymphocytes.

T-ALL represents approximately 15% of pediatric and 25% of adult ALL cases. While survival rates overall have improved during the last decade, 35 - 40% of patients with T-ALL still relapse, and treatment options are limited beyond first-line therapy.

The central dilemma in managing T-ALL lies in the remarkable resilience of leukemia cells. These cells defy programmed cell death by virtue of aberrant signaling mechanisms. Recent research has illuminated the potential of drugs that work by activating the death pathways of leukemia cells, leading to improvements in survival rates for patients with other forms of leukemia.

In preclinical research published in AACR’s Clinical Cancer Research, Dr. Stock conducted an early-phase clinical trial involving patients who had experienced relapses of ALL. The trial yielded promising results when a class of novel drugs was combined with conventional chemotherapy.

During Dr. Stock’s investigations into why some leukemia cells develop resistance to LP-118, she discovered that the resistant cells activated specific signaling pathways while simultaneously suppressing those responsible for cell death. To address this, Dr. Stock utilized targeted medications, such as Dasatinib, to block these growth-promoting signaling pathways, resulting in a marked increase in the sensitivity of the leukemia cells to LP-118, and, ultimately, cell death.

Building on these critical preclinical findings, Dr. Stock plans to combine LP-118, an exciting new drug with dual targeting activity to block proteins critical to the survival of T-ALL cellsmwith signaling pathway inhibitors like Dasatinib, or related drugs such as Ponatinib, in her Phase 1b/II trial.

This approach represents a strategic combination therapy designed to enhance the effectiveness of leukemia treatment in this patient population that is in urgent need of more options.

PHASE ONE is proud to partner with the Leukemia & Lymphoma Society and the Wise Family Foundation to fund Dr. Stock's pioneering research.

Research Update

In 2011, PHASE ONE funded a ground-breaking Phase I clinical trial led by Dr. Pedro Lowenstein and Dr. Maria Castro at the University of Michigan studying highly malignant brain tumors.

Despite constant developments in surgery, radiotherapy, and chemotherapy, a breakthrough for this particularly aggressive cancer had yet to be discovered. To address this pressing need, they created a new form of therapy combining gene therapy and immunotherapy to treat brain tumors.

This marked the first in human clinical trial combining tumor killing and immune stimulation. 

In 2023, the trial was finally completed showing promising results. 

Of the 18 patients in the study:
-Six lived for more than 2 years
-Three made it past 3 years
-And one patient is still alive after 5 years

These outcomes are a significant improvement over the current standard of care, which typically gives patients just over 14 months to live.

The new treatment also did not cause any harmful side effects, and revealed that the tumor-killing vector remained active for up to 17 months– not 1 month as anticipated. This breakthrough changes expectations and gives more time for the treatment to prevent the tumor from coming back. 

While further research is needed before using this treatment widely, the extended effectiveness of the Phase I trial suggests that it could significantly improve how these types of brain tumors are treated in the future. 

We know that investing in Phase I trials is playing the long game, and we are so grateful to play a part in this exciting breakthrough.

GRANT AMOUNT: $60,471

FORCE (Facing Our Risk of Cancer Empowered) has a longstanding history of furthering research for people facing cancer due to an inherited mutation, and for the past 25 years has been the voice for the hereditary cancer community.

Through education, support, advocacy, and research, FORCE improves the lives of millions of individuals and families facing hereditary breast, ovarian, pancreatic, prostate, colorectal, and endometrial cancers.

With support from PHASE ONE, FORCE will expand its Clinical Research Search & Enroll Program. Its goal is to ensure that all individuals who may benefit from participation in a study are informed and have equitable access to the information they need to make an informed personal decision.

The FORCE Clinical Research Search & Enroll tool helps individuals with a genetic mutation quickly identify studies unique to their situation. Last year, this tool was used by more than 6,700 people. In addition to the matching tool, FORCE raises awareness of the studies among the hereditary cancer population through multiple communication methods.

PHASE ONE’s Community Grant will enable FORCE to expand their research enrollment efforts with an improved capacity to identify new prospective studies for the hereditary cancer community, develop relevant, plain language summaries, and promote these studies through multiple communication channels.

A key focus is to syndicate research studies through their partnership program, which will allow cancer-specific nonprofits, and those serving underserved and minority populations, to highlight targeted studies relevant to their communities. Together, PHASE ONE and FORCE aim to further vital cancer research.

Insights from a Physician Leader

What recent developments or breakthroughs in cancer research do you find most exciting, and how do you see these impacting future patient care?

While overall the most impactful methods of decreasing cancer mortality have been advances in prevention and early detection, clearly the field of molecular oncology and precision medicine/immunotherapy – the targeted treatment of antibodies, mutated proteins and molecular pathways that are specific to an individual’s cancer – has revolutionized the medical treatment of cancer. The fact that the specific molecular biology of many cancers can be determined on biopsy or sometimes even by just a blood test (so-called “liquid biopsy”) has in tandem allowed for the development of targeted therapies to really take off.


How has the standard of care changed throughout the course of your career? And where do you think it's heading?

Cancer care has really revolutionized over the last two decades largely due to the proliferation of targeted therapies described above. Cancer treatment used to be the so-called nuclear option – a bomb going off in the body and we just hoped the patient could tolerate it. Now treatments are precise, tolerable, and malleable. Cancer – if not curable – can now often be thought of as a chronic disease, something one lives with, and lives well with for decades. Less toxic, oral cancer therapies have allowed that approach.Furthermore – cancer mutates over time. Targeted therapies have allowed an individual’s cancer treatment to change over time as their cancer changes. Another key aspect to this long term care approach is ensuring that treatment is patient-centered and carried out with full shared decision making with the patient and provider acting as a team. No care will be successful if the patient and their holistic life views are not front and center.

What do you think are the biggest opportunities for innovation in cancer research today, and what role does PHASE ONE play in supporting them?

AI clearly presents a new frontier of opportunity in cancer research. There are currently vast amounts of clinical and genomic data available. Machine learning algorithms can help mine this data to pair genomic biomarkers or potential molecular targets to existing therapy or to potentially new therapies on the horizon. Due to the limitations of traditional funding PHASE ONE can be of huge help to researchers who have been able to identify potential therapies through these means or who have identified therapies that already exist but could have novel applications. Funding for the latter is often scarce because pharmaceutical companies may have little incentive to fund an already FDA-approved drug.


What role do clinical trials play in cancer care, and why are they important to cancer research?

Research in humans is fundamental! There is no way to know if something that looks promising in a petri dish or a mouse will be safe and efficacious in humans. This applies not only to cancer therapies but also to diagnostic tools and prevention strategies. Furthermore, no one human is alike! Traditional clinical trial models are slow, costly and cumbersome and often cannot catch a cohort that is reflective of the sociodemographic of the disease. Clinical trial registries (databases that systematically collection information about individuals living with cancer including demographics, disease characteristics, treatments received and outcomes) are also pivotal because they foster collaboration, promote transparency and can allow researchers to work together to do population based research ultimately impacting standards of care and public policy.

Insights from a Young Oncologist

As someone just starting their career in the field of oncology, what recent developments or breakthroughs in cancer research do you find most exciting, and how do you see these impacting patient care in the future?

Like many oncologists, the numerous ways that we now harness the immune system are most exciting to me.

For example, drug development focusing on targeting signals unique to cancers, like CD19 in lymphoma, BCMA in mulitple myeloma, PSMA in prostate adenocarcinoma, Nectin-4 in renal cell carcinoma, to name just a few, have been combined with potent immune signals to stimulate a patient's own defenses against them or delivering potent chemotherapy directly to those tumors. Combining these immune strategies with more tolerable chemotherapy potentiates the response to either treatment, and has dramatically improved outcomes for patients.

There is a growing understanding of how cancer evades the immune system by subduing it or tricking it, and new treatment strategies are able to break down the defenses made by cancers to allow for better responses. Usually, these treatments are also more tolerable than their predecessors. I personally have had the opportunity to see these strategies tried in early phase trials at City of Hope, and watch as they have shrunk tumors and given new life to patients without other options.


What inspired you to pursue a career in oncology?

Hematology and Medical Oncology (Heme/Onc) is a specialty that can be pursued after a residency is done in Internal Medicine or Pediatrics. It is a partner discipline with Radiation Oncology and Surgical Oncology that usually focuses on delivering medical therapy, as opposed to radiation or surgery, to treat cancers.

Throughout my residency in Internal Medicine, I learned that the science within oncology was astonishing, with a new renaissance of thought and development. The partnership between patient, doctor, and the rest of the treatment team seemed most pure within the discipline of Heme/Onc, as there was such a concerted effort to align goals of treatment, expectations of the relationship throughout treatment, and the humility of treating cancers.

In very few areas of life or medicine are there conversations of the magnitude of cancer care. I have countless patients who showed me strength, grace, and wisdom as they pursued the long road of cancer treatment. There is a great need for doctors who focus on the clinical needs of cancer treatment, and a parallel need to contribute to ongoing clinical trials to treat cancer better in the future.

As a clinician scientist, you are encouraged to treat patients with the best available therapies. For many cancers, after one or two treatments, the best available therapies are toxic and ineffective, and our national cancer organizations recommend clinical trials instead of another mixture of chemotherapy. Participating in that research, and helping to develop the next best therapy is inspiring and absolutely necessary.

What do you think are the biggest opportunities for innovation in cancer research today, and what role does PHASE ONE play in supporting them?

It is overwhelming to imagine all of the opportunities for innovation in cancer research today.

There is a current interest in biologic therapies to harness the immune system or deliver highly potent drugs directly to tumors without injuring the healthy parts of the body normally affected by treatment. Up until recently, there have been many processes within cancer cells that were too difficult to design drugs that could interrupt those processes and hopefully improve cancer outcomes. Now the use of AI promises to discover the right compounds to target previously elusive parts of cancers.

There is also ongoing interest in detecting cancer earlier, with new strategies looking for the DNA of cancers in exceptionally small amounts within the bloodstream. Detecting cancers earlier will likely prevent cancer deaths, though this is still a work in progress. The major limitation to cancer treatment innovation is that new treatment strategies are difficult to develop, and investment in early research is likely to favor "known" concepts.

PHASE ONE promises to invest in big ideas across the spectrum of cancer, from management of early surgical cases to very advanced cancers. By supporting new concepts, we can contribute to a snowballing effect (though in LA probably a mudslide) of scientific concepts that can generate interest, iteration and ultimately later phase trials that will create new opportunities for cancer therapy.


What role do clinical trials play in cancer care, and why are they important to cancer research?

Fortunately and unfortunately, our intuition is not sufficient to determine what will be a good cancer treatment. In the past, higher doses of chemotherapy were pursued to the point of emptying the bone marrow with improvements only in a few cancer subtypes under specific situations. We have learned that different cancers have different drives, causing them to respond to hormones in some cases, immune stimulation in others, and occasionally should be left alone as treatment can worsen them. We never know the answers to any of these clinical situations without diligent clinical trials.

Clinical trials pose questions, from simple to bold, but the main objective is to ask "does this strategy, in this situation, help this group of patients?" Without a specific question, we risk prescribing treatments and recommending strategies that have minimal positive effects, or even harm our patients.

Clinical trials also spark new questions. Sometimes we find surprises within the group that we study, and those can create whole new fields of understanding and interest. Like predicting who may win a championship, or writing a hit song, or producing a viral video, there are concepts that are always guiding success in a field, but each generation brings new approaches.