On March 15, 2021, Rubius Therapeutics, Inc. (the “Company”)
announced initial clinical, pharmacodynamic and tumor trafficking data from its ongoing Phase 1/2 clinical trial of RTX-240 in
patients with advanced solid tumors. The Company also shared tumor trafficking data from one patient with relapsed/refractory acute
myeloid leukemia (AML) in the second Phase 1 arm of the study. The Company believes these data provide initial proof-of-concept
of the RED PLATFORM® by providing evidence that red blood cells can be engineered to mimic the human immune system
and stimulate adaptive and innate immunity to generate clinical responses in cancer patients with refractory disease.
Initial Efficacy Data
Five (5) dose cohorts were completed in the solid tumor trial
at the time of the data cutoff on February 28, 2021 (n=16), with 16 patients evaluable for safety (primary outcome measure) and
15 patients evaluable for efficacy (secondary outcome measure) based on RECIST v1.1.
The study is continuing to enroll patients and despite the fact
that dose optimization is still ongoing, RTX-240 generated:
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A confirmed partial response (PR) with a 54% reduction in the target lesions at the 1e8 dose administered every 4 weeks in
a patient with metastatic anal cancer whose disease had progressed on anti-PD-L1 therapy. Treatment of this patient was ongoing
8 months following the first dose at data cutoff;
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An unconfirmed PR with complete resolution of the target hepatic lesion and resolution of 14/15 hepatic lesions at the 1e10
dose administered every 4 weeks in a patient with metastatic uveal melanoma whose disease had progressed on anti-PD-1 therapy;
Treatment of this patient was ongoing 4 months following the first dose at data cutoff; and
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Stable disease (SD) was observed in 6 patients, including 4 individual patients with stable disease for at least 12 weeks:
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Non-small cell lung cancer (disease stabilization for 12 weeks with treatment ongoing as of the data cutoff);
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Soft tissue sarcoma (disease stabilization for 4 months);
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Pancreatic cancer (disease stabilization for 3 months); and
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Prostate cancer (disease stabilization for 4 months).
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Initial Safety Data
The most common treatment-related Grade 1/2 adverse events were
fatigue (n=4), chills, nausea, decreased appetite and arthralgias all reported in 3 patients each. There were no treatment-related
Grade 3/4 adverse events, no dose-limiting toxicities and a single Grade 1 event of liver toxicity.
Ten (10) immune-related adverse events (irAE) were observed
among 5 patients with no reported treatment-related Grade 3/4 irAEs. Grade 2 treatment-related irAEs included pneumonitis (n=1),
adrenal insufficiency (n=1) and hypothyroidism (n=1).
Pharmacodynamic Data
In addition to evaluating safety and preliminary efficacy data,
the trial is evaluating the pharmacodynamic effects of RTX-240:
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RTX-240 stimulated innate and adaptive immunity as demonstrated by the activation and/or expansion of NK or memory CD8+ T cells
in all patients, with 9/16 patients showing activation and expansion in both cell types. There was an overall trend towards a dose
response in absolute NK cell numbers (expansion);
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Detailed NK cell analysis showed an increased percentage of CD16+CD56dim (mature NK cells) and CD56bright
(immature NK cells) across dose levels
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These cell subtypes are associated with cytotoxicity and cytokine production respectively; and
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RTX-240 induced expression of key NK cell activation receptors, including NKp30 and the ratio of cells expressing the activation
receptor NKG2D versus the inhibitory receptor NKG2A.
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This specific signature of NK cell receptor expression may allow selection of specific tumor types with predicted sensitivity
to RTX-240.
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Tumor Infiltration Data
Immune cell trafficking into the tumor microenvironment (TME)
was assessed by tumor biopsies from participating patients with solid tumors (optional; n=4) and AML (standard of care; n=1).
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Trafficking of T and NK cells into the TME was observed in 3/5 patients (1.6 to 10-fold increases), including one patient each
with metastatic mesothelioma, metastatic soft tissue sarcoma and refractory AML. Tumor infiltration was not observed in patients
with ovarian cancer (n=1) and heavily pretreated melanoma (n=1);
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There was increased expression of PD-L1 observed in 3/4 patients with solid tumors, suggesting an improved immune-permissive
TME; and
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In one patient with AML, trafficking of T and NK cells into the bone marrow was associated with increases in the cellularity
of the marrow.
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A copy of the press release issued in connection with the announcement
is being furnished as Exhibit 99.1 to this Current Report on Form 8-K. A copy of the Company’s presentation to be shared
with investors and others from time to time in connection with today’s announcement is filed as Exhibit 99.2 to this Current
Report on Form 8-K and is incorporated by reference herein.
The information in Exhibit 99.1 attached hereto is intended
to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934,
as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated
by reference in any filing under the Securities Act of 1933, as amended or the Exchange Act, except as expressly set forth by specific
reference in such filing.
Forward Looking Statements
This report contains forward-looking statements within the meaning
of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the Company’s
expectations with respect to the therapeutic potential of its pipeline of Red Cell Therapeutics, including RTX-240, its expectations
regarding the timing, enrollment, data from and success of the future cohorts and phases of the clinical trial of RTX-240, including
the Phase 1/2 clinical trial of RTX-240, its plans to initiate a RTX-240 Phase 2 expansion cohort, an RTX-240 Phase 1 clinical
trial in combination with an anti-PD-1 therapy in advanced solid tumors and file an Investigational New Drug application for RTX-224
over the next twelve months, its expectations regarding the biological effects of RTX-240 on innate and adaptive immunity and the
related therapeutic benefits, its expectations regarding the initial preliminary data from RTX-240 and the related therapeutic
benefits and validation of its RED PLATFORM and its expectations regarding its strategy, business plans and focus. The words “may,”
“will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,”
“intend,” “believe,” “estimate,” “predict,” “project,” “potential,”
“continue,” “target” and similar expressions are intended to identify forward-looking statements, although
not all forward-looking statements contain these identifying words. Any forward-looking statements in this report are based on
management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that
may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained
in this report, including, without limitation, those risks and uncertainties related to the development of the Company’s
Red Cell Therapeutic product candidates and their therapeutic potential and other risks identified in the Company’s SEC filings,
including its Annual Report on Form 10-K for the year ended December 31, 2020, and subsequent filings with the SEC and
risks and uncertainties related to the severity and duration of the impact of COVID-19 on our clinical trials, business and operations.
We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We
disclaim any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions
or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from
those set forth in the forward-looking statements. Any forward-looking statements contained in this report release represent our
views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. We explicitly
disclaim any obligation to update any forward-looking statements.