Five Prime Therapeutics (FPRX) provided an overview of five assets, one in a pivotal Phase III trial
(bemarituzumab), one in a Phase II trial (cabiralizumab) and three others in Phase I development.
Bemarituzumab (bema) is a first-in-class antibody specific for FGFR2b, a splice variant of the
fibroblast growth factor receptor FGFR2 expressed on tumor cells. Bema blocks growth factor
binding to FGFR2b and also targets the tumor cells for killing by ADCC. FGFR2 gene amplification
is seen in about 10% of gastric cancer patients and is associated with significantly reduced
survival (2-year OS of 48.1% vs 19.8%). A pivotal Phase III trial (FIGHT) was initiated in September
2018 and is evaluating Bema + chemotherapy (modified FOLFOX6) compared to placebo +
chemotherapy in front-line FGFR2B overexpressing gastric cancer and gastroesophageal junction
(GEJ) cancer. Safety lead-in data for this trial is expected next week at the ASCO-GI meeting.
Cabiralizumab (cabira) is an antibody that blocks the Colony Stimulating Factor 1 Receptor (CSF1-
R) present on tumor activated macrophages (TAMs) and is being developed in collaboration with
BMS. Binding of cabira to CSF1-R leads to depletion of TAMs. Similar to PD-L1 on tumor cells but
using a different mechanism, TAMs can inhibit cytotoxic T cells and high TAM levels are
associated with poor prognosis in pancreatic and other cancers. In March 2018, BMS initiated an
open label Phase II study of cabira administered in combination with Opdivo with and without
chemotherapy in patients with second-line pancreatic cancer. This study is expected to complete
enrollment in 2019 (40 patients in each of 4 arms) and is designed to generate data supporting a
front-line or second-line pivotal study. In 2018 BMS also expanded cabira development within
pancreatic (including combinations with radiotherapy, anti-CD40 antibodies or gemcitabine) and
into other tumor settings (including melanoma, NSCLC, RCC and in January 2019, biliary tract
cancer).
FPA150 is an antibody that inhibits activity of B7-H4, a checkpoint inhibitor that is related to PDL1 and is present on tumor cells. This first-in-class therapy is wholly owned by Five Prime. B7-H4
is expressed in multiple solid tumors that are not well served by current checkpoint inhibitors.
Moderate to high levels of B7-H4 have been reported in approximately 60% of patients with
breast cancer and 50% of patients with ovarian and endometrial cancer. There is very little
expression on normal tissue. FPA150 is currently being evaluated in a Phase Ia/Ib trial evaluating
monotherapy activity in patients with B7-H4 overexpressing tumors. Phase Ia dose escalation
was initiated in March 2018 (any solid tumor) and an exploratory cohort with a basket of B7-H4
overexpressing tumors was initiated in October 2018. Once an optimal dose has been identified
(1H of 2019), the trial will expand to Phase Ib and will enroll patients with breast (HR+/HER2- and
TNBC), ovarian and endometrial cancers with B7-H4 overexpression. Data from the dose
escalation cohort will be presented at ASCO (Q2 2019) while data from the exploratory cohort is
expected to be presented at ESMO (Q4 2019).
FPT155 is a first-in-class CD80-Fc fusion protein. CD80 is a co-stimulatory molecule expressed on
antigen presenting cells and which binds CD28 on T cells to provide the co-stimulatory signal
required for T cell activation (in addition to MHC-TCR binding). FPT155 is designed to bind the
antigen presenting cell (through the IgG1 Fc moiety) and CD-28 present on T cells to enhance costimulation of T cells without superagonism. A Phase Ia/Ib trial initiated in Australia in November
2018 enrolling patients with any solid tumor to look for monotherapy activity. An exploratory
cohort with a basket of solid tumors is planned and once an optimal dose is identified the trial will
expand to Phase Ib with select solid tumor cohorts. Phase I data will be presented at a medical
conference in 2H 2019.
The final asset presented was BMS-986258 an antibody to TIM3 licensed to BMS. TIM3 is an
immune checkpoint receptor and BMS-986258 was designed to block interaction between TIM3
and phosphatidylserine, a key lipid found in the tumor microenvironment. A Phase I/II clinical
trial initiated in March 2018 and starts with a dose escalation of BMS-986258 (arm A), BMS986258 + rHuPH20 (arm A1) and BMS-986258 + Opdivo (arm B). The Phase II portion of the trial
will evaluate BMS-986258 + Opdivo (arm C). BMS-986258 is the first of three candidates from
the IO research collaboration with BMS. The collaboration provides for up to $300 million in
milestone payments per collaboration product and tiered royalties.
As of December 31st 2018, Five Prime has $270 million in cash, cash equivalent and marketable
securities. FY 2019 operating activities are estimated at $117-122 million and EOY 2019 cash is
estimated at $148-153 million not including any milestone payments.
(bemarituzumab), one in a Phase II trial (cabiralizumab) and three others in Phase I development.
Bemarituzumab (bema) is a first-in-class antibody specific for FGFR2b, a splice variant of the
fibroblast growth factor receptor FGFR2 expressed on tumor cells. Bema blocks growth factor
binding to FGFR2b and also targets the tumor cells for killing by ADCC. FGFR2 gene amplification
is seen in about 10% of gastric cancer patients and is associated with significantly reduced
survival (2-year OS of 48.1% vs 19.8%). A pivotal Phase III trial (FIGHT) was initiated in September
2018 and is evaluating Bema + chemotherapy (modified FOLFOX6) compared to placebo +
chemotherapy in front-line FGFR2B overexpressing gastric cancer and gastroesophageal junction
(GEJ) cancer. Safety lead-in data for this trial is expected next week at the ASCO-GI meeting.
Cabiralizumab (cabira) is an antibody that blocks the Colony Stimulating Factor 1 Receptor (CSF1-
R) present on tumor activated macrophages (TAMs) and is being developed in collaboration with
BMS. Binding of cabira to CSF1-R leads to depletion of TAMs. Similar to PD-L1 on tumor cells but
using a different mechanism, TAMs can inhibit cytotoxic T cells and high TAM levels are
associated with poor prognosis in pancreatic and other cancers. In March 2018, BMS initiated an
open label Phase II study of cabira administered in combination with Opdivo with and without
chemotherapy in patients with second-line pancreatic cancer. This study is expected to complete
enrollment in 2019 (40 patients in each of 4 arms) and is designed to generate data supporting a
front-line or second-line pivotal study. In 2018 BMS also expanded cabira development within
pancreatic (including combinations with radiotherapy, anti-CD40 antibodies or gemcitabine) and
into other tumor settings (including melanoma, NSCLC, RCC and in January 2019, biliary tract
cancer).
FPA150 is an antibody that inhibits activity of B7-H4, a checkpoint inhibitor that is related to PDL1 and is present on tumor cells. This first-in-class therapy is wholly owned by Five Prime. B7-H4
is expressed in multiple solid tumors that are not well served by current checkpoint inhibitors.
Moderate to high levels of B7-H4 have been reported in approximately 60% of patients with
breast cancer and 50% of patients with ovarian and endometrial cancer. There is very little
expression on normal tissue. FPA150 is currently being evaluated in a Phase Ia/Ib trial evaluating
monotherapy activity in patients with B7-H4 overexpressing tumors. Phase Ia dose escalation
was initiated in March 2018 (any solid tumor) and an exploratory cohort with a basket of B7-H4
overexpressing tumors was initiated in October 2018. Once an optimal dose has been identified
(1H of 2019), the trial will expand to Phase Ib and will enroll patients with breast (HR+/HER2- and
TNBC), ovarian and endometrial cancers with B7-H4 overexpression. Data from the dose
escalation cohort will be presented at ASCO (Q2 2019) while data from the exploratory cohort is
expected to be presented at ESMO (Q4 2019).
FPT155 is a first-in-class CD80-Fc fusion protein. CD80 is a co-stimulatory molecule expressed on
antigen presenting cells and which binds CD28 on T cells to provide the co-stimulatory signal
required for T cell activation (in addition to MHC-TCR binding). FPT155 is designed to bind the
antigen presenting cell (through the IgG1 Fc moiety) and CD-28 present on T cells to enhance costimulation of T cells without superagonism. A Phase Ia/Ib trial initiated in Australia in November
2018 enrolling patients with any solid tumor to look for monotherapy activity. An exploratory
cohort with a basket of solid tumors is planned and once an optimal dose is identified the trial will
expand to Phase Ib with select solid tumor cohorts. Phase I data will be presented at a medical
conference in 2H 2019.
The final asset presented was BMS-986258 an antibody to TIM3 licensed to BMS. TIM3 is an
immune checkpoint receptor and BMS-986258 was designed to block interaction between TIM3
and phosphatidylserine, a key lipid found in the tumor microenvironment. A Phase I/II clinical
trial initiated in March 2018 and starts with a dose escalation of BMS-986258 (arm A), BMS986258 + rHuPH20 (arm A1) and BMS-986258 + Opdivo (arm B). The Phase II portion of the trial
will evaluate BMS-986258 + Opdivo (arm C). BMS-986258 is the first of three candidates from
the IO research collaboration with BMS. The collaboration provides for up to $300 million in
milestone payments per collaboration product and tiered royalties.
As of December 31st 2018, Five Prime has $270 million in cash, cash equivalent and marketable
securities. FY 2019 operating activities are estimated at $117-122 million and EOY 2019 cash is
estimated at $148-153 million not including any milestone payments.
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