Pipeline

We employ biologics that are designed to enhance the ability of the patient’s own immune system to detect and destroy cancer cells. Our two lead molecules, TTI-621 and TTI-622, are innate immune checkpoint inhibitors targeting CD47.

PROGRAM

INDICATION

COMBINATION AGENT

STAGE OF DEVELOPMENT

PRECLINICAL

IND ENABLING

EARLY-STAGE CLINICAL

LATE-STAGE CLINICAL

SPONSOR

STATUS

622

Carfilzomib+dex

EARLY-STAGE CLINICAL

Enrolling

622

AML p53 mut.

Azacitidine

EARLY-STAGE CLINICAL

Enrolling

622

AML unfit

Aza+Ven

EARLY-STAGE CLINICAL

Enrolling

622

DLBCL (IST)

PD-1

IND ENABLING

Initiate P1b/2 in 4Q21 – 1H22

622

Ovarian

Chemotx

IND ENABLING

Initiate P1b/2 in 2H21

622

[Solid tumor #2]

[TBA]

IND ENABLING

Initiate P1b/2 in 1H22

621

PTCL

— [Monotx]

EARLY-STAGE CLINICAL

Initiate P2 in 2H21

621

DLBCL (IST)

PD-1

IND ENABLING

Initiate P1b/2 in 4Q21-1H22

621

Leiomyosarcoma

Doxorubicin

IND ENABLING

Enrolling

Additional studies:

622 Q2/3W dose escalation study in lymphomas (enrolling)
621 Q2/3W dose escalation study in CTCL (enrolling)
622 & 621 in combination with daratumumab P1b/2 IST in multiple myeloma (initiate in 2H21); Memorial Sloan Kettering

Abbreviations: Aza+Ven – Azacitidine + Venetoclax; AML – Acute Myeloid Leukemia; dex – dexamethasone; DLBCL – Diffuse Large B-Cell Lymphoma; IST – Investigator-Sponsored Trial; MM – Multiple Myeloma; PTCL – Peripheral T-Cell Lymphoma; TBA – To Be Announced

Pipeline

Target

Indication

Cancer

DiscoveryPreclinicalPhase 1aPhase 1b/2

Target

Undisclosed – immuno-oncology Targets

Candidate

Undisclosed

Indication

Cancer

DiscoveryPreclinicalPhase 1aPhase 1b/2

TTI-622

TTI-622 consists of the same extracellular CD47-binding domain of human SIRPα as TTI-621 but has an IgG4 Fc region instead of an IgG1 Fc.

The IgG4 Fc region of TTI-622 has more limited interactions with Fc receptors than IgG1, and thus TTI-622 is predicted to deliver a moderate “eat me” signal to macrophages. We therefore expect to achieve higher levels of TTI-622 in patients compared to TTI-621, leading to greater and more sustained CD47 blockade. Thus, TTI-622 will allow us to assess how higher CD47 blockade with an IgG4-based agent in patients compared to lower CD47 blockade with the IgG1-based TTI-621. Importantly, TTI-622 has been shown not to bind appreciably to human red blood cells, unlike many other CD47 blocking agents.

TTI-622 is being studied in a two-part, multicenter, open-label, phase 1a/1b study in patients with advanced relapsed or refractory lymphoma or multiple myeloma (NCT03530683). In the phase 1a dose-escalation part, patients are being enrolled in sequential dose cohorts to receive TTI-622 once weekly to characterize safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose. In the phase 1b part, patients will be treated with TTI-622 in combination with other agents.

TTI-621

Intravenously administered TTI-621 is currently being evaluated in a multicenter, open-label phase 1 trial in patients with relapsed/refractory hematologic malignancies (TTI-621-01; NCT02663518). The study consists of four parts: (a) completed Parts 1-3 in hematologic malignancies, with dosing up to 0.5 mg/kg; and (b) ongoing Part 4 in cutaneous T-cell lymphoma patients, utilizing revised dose-limiting toxicity (DLT) criteria for thrombocytopenia and an amended protocol to allow for dosing above 0.5 mg/kg. Parts 1-3 involved over 200 patients receiving doses ranging from 0.05 to 0.5 mg/kg. TTI-621 was generally well tolerated with the most frequent drug related adverse events being low grade infusion reactions and transient thrombocytopenia that was not associated with bleeding. Importantly, monotherapy activity was observed in patients across a range of hematologic malignancies, including cutaneous T-cell lymphoma, peripheral T-cell lymphoma, and diffuse large B-cell lymphoma. Notably, most patients were at an advanced stage of their disease and heavily pretreated.

More details of this study can be found in the Patients section.

An exploratory study evaluating the use of TTI-621 in solid tumors is also being planned.

TTI-621 was evaluated as an intratumoral agent in a multicenter, open-label phase 1b/2 study in patients with relapsed and refractory solid tumors and mycosis fungoides, the most common form of cutaneous T cell lymphoma (Study TTI-621-02; NCT02890368). Intratumoral TTI‐621 was well tolerated and reduction in CAILS scores, which measures local lesion responses, was observed in the majority of patients. These responses occurred rapidly within two weeks of first administration. Having served its purpose of providing clinical proof-of-concept this trial has been closed and we are now focused on intravenous delivery of TTI-621.

TTI-621 has been extensively tested in preclinical laboratory studies. Key findings from these studies are summarized below:

UNDISCLOSED TARGETS

Efforts to discover novel cancer therapeutic targets are ongoing. We are applying our expertise in biologics and medicinal chemistry to generate novel, patentable compounds against undisclosed immuno-oncology targets.

Pipeline

Pipeline

CD47 – Innate Immune Checkpoint

TTI-622

Heme malignancies

TTI-622

Solid tumors

TTI-621

Heme malignancies

TTI-621

Solid tumors

STING Agonist

TTI-10001

Cancer

Undisclosed – immuno-oncology Targets

Undisclosed

Cancer

TTI-622

TTI-621

UNDISCLOSED TARGETS

Cambridge Office

Mississauga Office

INVESTOR RELATIONS

GENERAL