Our lead product candidate, ALRN-6924 mimics the p53 tumor suppressor protein to disrupt its interactions with both its endogenous inhibitors, MDMX and MDM2. For p53 wild-type tumors, ALRN-6924 can restore p53-dependent tumor suppression. ALRN-6924 is currently being evaluated in multiple clinical trials for the treatment of solid and hematological cancers, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and peripheral T-cell lymphoma (PTCL).  Preliminary clinical results have demonstrated a favorable safety profile and evidence of antitumor activity and duration of effect.

Our ongoing clinical trials of ALRN-6924 include:

  • Phase 1 trial for the treatment of advanced solid tumors or lymphomas

  • Phase 2a trial for the treatment of peripheral T-cell lymphoma (PTCL)

  • Phase 1 trial for the treatment of acute myeloid leukemia (AML), and advanced myelodysplastic syndrome (MDS), as a monotherapy

  • Phase 1b trial for the treatment of AML/MDS in combination with cytosine arabinoside (Ara-C)

For more information, access our ongoing trial updates at ClinicalTrials.gov.

We are committed to building a pipeline of novel stabilized cell-permeating peptide therapeutics to improve outcomes for patients with difficult-to-treat cancers and other diseases. Our lead product candidate ALRN-6924 mimics the p53 tumor suppressor protein. P-53 is long known as “the guardian of the genome” and is the body’s first line of defense against cancer.

ALRN-6924 is currently in multiple clinical trials in various cancer indications. Our ongoing clinical trials of ALRN-6924 consist of a Phase 1 trial for the treatment of advanced solid tumors or lymphomas, a Phase 2a trial for the treatment of peripheral T-cell lymphoma, or PTCL, a Phase 1 trial for the treatment of acute myeloid leukemia, or AML, and advanced myelodysplastic syndrome, or MDS, as a monotherapy and a Phase 1b trial for the treatment of AML/MDS in combination with cytosine arabinoside, or Ara-C.

Peripheral T-Cell Lymphoma

Lymphoma is the most common blood cancer and it primarily occurs when lymphocytes, a type of white blood cell, grow abnormally and accumulate in one or more lymph nodes. The body has two main types of lymphocytes that can develop into lymphomas: B-lymphocytes, or B-cells, and T-lymphocytes, or T-cells. PTCL comprises a group of rare and aggressive non-Hodgkin lymphomas, or NHL, that develop from mature T-cells. According to the Leukemia and Lymphoma Society, PTCL accounts for approximately 10% to 15% of all NHL cases in the United States, which suggests that 7,200 to 10,800 new cases of PTCL are diagnosed in the United States annually. In a study by the International T-cell Lymphoma Project, overall survival in the most common subtypes of PTCL, PTCL not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma, at five years was only 32%.

For most subtypes of PTCL, the front-line treatment is typically a combination chemotherapy regimen, such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), or other multi-drug chemotherapeutic regimens. While over 50% of patients initially respond to these chemotherapeutic regimens, many patients with PTCL do not respond to these regimens or, after initially responding, later relapse. For second-line treatment, some oncologists recommend treating relapsed patients with a variety of intensive combination chemotherapy therapies, such as ICE (ifosfamide, carboplatin, etoposide), followed by an autologous stem cell transplant. Alternatively, patients with relapsed/refractory PTCL may be treated with the chemotherapeutic antifolate pralatrexate (Folotyn), the antiCD30 antibody-drug conjugate brentuximab vedotin (Adcetris) or the histone deacetylase, or HDAC, inhibitors romidepsin (Istodax) and belinostat (Beleodaq) or a combination of a chemotherapy and one of the HDAC inhibitors. However, these treatments also have demonstrated limited efficacy and tolerability.

Acute Myeloid Leukemia and Myelodysplastic Syndromes

AML is a cancer of the myeloid line of blood cells, characterized primarily by the rapid growth of abnormal white blood cells that build up in the bone marrow and interfere with the production of normal blood cells. We believe that a total of approximately 41,000 new cases of AML are diagnosed each year in the United States, France, Germany, Italy, Spain, the United Kingdom and Japan. Survival is age-dependent and survival rates are extremely poor for the elderly. According to the U.S. National Cancer Institute, in the United States, while the five-year relative survival for AML patients age 20 to 49 years is 55%, it is only 6% for patients that are 65 years or older. MDS is a group of diverse bone marrow disorders in which the bone marrow does not produce enough healthy blood cells. MDS is often referred to as a “bone marrow failure disorder.” The American Cancer Society, or ACS, estimates that there are 13,000 new MDS cases each year in the United States. AML and MDS are often treated similarly in clinical practice because both disorders can originate from the same cell type and have other features in common. As a result, it is difficult to distinguish between AML and MDS. Irrespective of diagnostic challenges, about one third of MDS patients progress to AML.

The front-line treatment for patients with AML is typically a combination chemotherapy, such as intensive Ara-C-based induction chemotherapy followed by Ara-C-based consolidation therapy. Because Ara-Cbased induction chemotherapies have significant toxicities, elderly patients with AML typically do not qualify for those therapies. We estimate that only approximately 57% of elderly patients receive front-line treatment for AML and that approximately 20% receive second-line treatment. Instead, elderly patients are treated with palliative measures encompassing best supportive care, low-dose Ara-C, or hypomethylating agents such as decitabine (Dacogen) or azacitidine (Vidaza), or they are referred to clinical trials with investigational agents. Once elderly patients experience disease progression following their initial treatment, they have a very poor expected survival rate and treatment represents a significant medical challenge. Many elderly patients go untreated after failure of these treatment options. Over the past two decades, many compounds have been evaluated in elderly patients with AML, but due to significant toxicities and/or lack of efficacy, only one new treatment with limited application has been specifically approved for AML.

To learn more about Aileron Therapeutics’ clinical trials, please visit clinicaltrials.gov.