Executive Summary

Q4 2016 delivered the company’s first revenue recognition of $0.32M from its research collaboration, while operating loss narrowed sequentially as R&D stepped down after a Q3 milestone payment; cash and marketable securities ended the year at $83.59M, funding operations into mid‑2018 .
2017 operating expense guidance set at approximately $50M cash‑based non‑GAAP OpEx, with near‑term catalysts: SY‑1365 (CDK7 inhibitor) Phase 1 initiation in Q2 2017 and initial SY‑1425 (tamibarotene) Phase 2 data in fall 2017 .
Strategic execution advanced: SY‑1425 Phase 2 enrollment began in September; an IDE for the companion assay was cleared in Q4 enabling expansion into newly diagnosed AML (elderly/unfit) and lower‑risk transfusion‑dependent MDS cohorts .
Management emphasized platform leadership and pipeline momentum: “2016 was a year of tremendous progress,” positioning for “a breakthrough 2017” as the team advances two lead programs and expands preclinical efforts .

What Went Well and What Went Wrong

First revenue recognized: $0.317M from a research agreement, reflecting completion‑based revenue recognition; no revenue was recognized in the first nine months of 2016 .
Pipeline execution: Enrollment initiated for SY‑1425 Phase 2 in September 2016; IDE approval in Q4 enabled expansion to additional AML/MDS segments; initial data guided for fall 2017 .
Clear 2017 plan and spend guidance: Management set 2017 cash‑based non‑GAAP operating expenses at ~ $50M and outlined key 2017 milestones; CEO Nancy Simonian: “2016 was a year of tremendous progress… [laying] the groundwork for a breakthrough 2017” .

Continued operating losses with no product revenue: Q4 net loss of $(10.97)M (vs. $(10.69)M YoY), reflecting the early‑stage biotech profile without marketed products .
Sequential revenue visibility remains limited: Q4 revenue was a one‑time recognition on project completion under the research agreement; management noted revenue is recognized upon completed performance, not ratably .
Prior quarter expense spike highlights variability: Q3 R&D was elevated by a $1.0M licensing milestone to TMRC on first dosing in SY‑1425 Phase 2; while Q4 R&D stepped down, the quarter‑to‑quarter variability underscores milestone‑driven cost swings .

Metric	Q4 2015	Q2 2016	Q3 2016	Q4 2016
Revenue ($M)	$0.00	$0.00	$0.00	$0.32
R&D Expense ($M)	$8.38	$9.53	$11.58	$8.44
G&A Expense ($M)	$2.31	$2.54	$2.63	$2.92
Total Operating Expenses ($M)	$10.69	$12.07	$14.22	$11.36
Loss from Operations ($M)	$(10.69)	$(12.07)	$(14.22)	$(11.05)
Net Loss ($M)	$(10.69)	$(12.02)	$(14.17)	$(10.97)
Diluted EPS ($)	$(5.14)	$(5.42)	$(0.65)	$(0.47)
Cash, Cash Equivalents & Marketable Securities ($M)	$35.91 (12/31/15)	$50.12 (6/30/16)	$93.49 (9/30/16)	$83.59 (12/31/16)

Notes:

Q3 2016 R&D included a $1.0M milestone to TMRC upon successful first patient dosing in SY‑1425 Phase 2, contributing to the sequential step down in Q4 R&D after that payment .
Q4 2016 revenue was recognized upon completion criteria under the research agreement; 2016 full‑year revenue totaled $0.3M .

No segments are reported; KPIs focus on pipeline milestones and cash runway.

Metric	Period	Previous Guidance	Current Guidance	Change
Cash‑based non‑GAAP Operating Expenses	FY 2017	Not previously quantified	~ $50M	New quantitative guide
Cash Runway	Through mid‑2018	Through mid‑2018 (post‑IPO)	Through mid‑2018	Maintained
SY‑1365 Phase 1 Start	1H 2017	1H 2017	Q2 2017	Narrowed timing
SY‑1425 initial Phase 2 data	Fall 2017	N/A	Fall 2017	New timing disclosure

(Transcript not found in our database for Q4 2016; themes synthesized from the Q4 8‑K press release and FY2016 10‑K.)

Topic	Previous Mentions (Q2–Q3)	Current Period (Q4 2016)	Trend
SY‑1425 clinical execution	IND accepted; Phase 2 enrollment plan; RARA biomarker strategy	Enrollment initiated in Sep; IDE approved in Q4 enabling expansion to elderly/unfit AML and lower‑risk MDS; initial data fall 2017	Advancing on plan
Companion diagnostic/assay	Biomarker strategy described	IDE approved for assay in Q4; pursuing CLIA test with commercial provider	Derisked diagnostic path
SY‑1365 CDK7 program	IND‑enabling complete; Phase 1 targeted 1H17	Phase 1 planned Q2 2017; initial data 1H18	On track to clinic
Spend & runway	IPO proceeds; funding into mid‑2018	2017 cash OpEx guide ~$50M; runway into mid‑2018 reiterated	Clearer spend framework
Platform expansion	Preclinical programs highlighted	Four early preclinical programs; intent to file at least one IND in 2019	Broadening

“2016 was a year of tremendous progress as we transitioned Syros to a clinical‑stage and publicly listed company… These accomplishments lay the groundwork for a breakthrough 2017” — Nancy Simonian, M.D., CEO .
“In just three years, we’ve grown from a research‑driven startup to a clinical‑stage company with multiple programs in the pipeline” — Nancy Simonian, M.D. .

We did not locate a Q4 2016 earnings call transcript in our document set; no analyst Q&A themes were available to summarize (we searched for earnings‑call‑transcript between Dec 1, 2016 and Mar 31, 2017 and found none) [ListDocuments result].

Wall Street consensus (S&P Global/Capital IQ) EPS and revenue estimates were unavailable due to missing CIQ mapping for SYRS in our tool; as a result, we cannot benchmark Q4 revenue or EPS vs. consensus (GetEstimates returned a mapping error). Values retrieved from S&P Global were unavailable.

Cash runway and spend visibility: Year‑end cash and marketable securities of $83.59M support operations into mid‑2018; 2017 cash‑based non‑GAAP OpEx guided to ~ $50M, providing clarity on funding and burn .
Near‑term data and initiation catalysts: Initial SY‑1425 Phase 2 readout (fall 2017) and SY‑1365 Phase 1 initiation (Q2 2017) are key stock catalysts in 2017–2018; early success could re‑rate the program optionality .
Clinical execution momentum: Q4 marked IDE approval for the SY‑1425 companion assay and expansion to additional AML/MDS cohorts, a notable de‑risking of the biomarker‑driven strategy .
Expense variability likely around milestones: The Q3‑to‑Q4 R&D step down reflects the one‑time $1.0M milestone paid in Q3; future milestones may again create quarterly expense variability .
Early revenue is collaboration‑based: Q4 revenue ($0.32M) stemmed from completion‑based recognition under the research agreement; ongoing revenue visibility remains limited absent product launches .
Valuation inflection hinges on clinical readouts: With no commercial products, shares are most sensitive to clinical data quality and timelines in SY‑1425 and SY‑1365; risk‑reward turns on execution against 2017/2018 milestones .

KPI / Milestone	Status
SY‑1425 Phase 2 enrollment	Initiated Sep 2016
SY‑1425 companion assay IDE	Approved in Q4 2016; supports trial expansion
SY‑1425 initial data	Fall 2017 planned
SY‑1365 Phase 1 start	Planned Q2 2017
SY‑1365 initial data	Planned 1H 2018
Year‑end cash & marketable securities	$83.59M (12/31/16)
Cash runway	Into mid‑2018

Search and document coverage notes:

Q4 2016 8‑K (Item 2.02) and press release (Ex. 99.1) reviewed in full .
FY2016 10‑K used for selected quarterly financials and pipeline details .
Q2 2016 8‑K press release (for prior period context) reviewed .
No Q4 2016 earnings call transcript was found in our corpus for the period searched (Dec 1, 2016–Mar 31, 2017).